phkineticaФармакокинетика и ФармакодинамикаPharmacokinetics and Pharmacodynamics2587-78362686-8830ООО «Издательство ОКИ»phkinetica-104Research ArticleАКТУАЛЬНЫЕ ОБЗОРЫCURRENT REVIEWSБиотрансформация и фармакокинетика морфолинсодержащих лекарственных препаратовБастрыгинД. В.noemail@neicon.ruКолывановГ. Б.noemail@neicon.ruЖердевВ. П.noemail@neicon.ruФГБУ «НИИ фармакологии имени В.В. Закусова» РАМН, МоскваRussian Federation20120903201201317Copyright © Бастрыгин Д.В., Колыванов Г.Б., Жердев В.П., 20122012Бастрыгин Д.В., Колыванов Г.Б., Жердев В.П.Бастрыгин Д.В., Колыванов Г.Б., Жердев В.П.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacokinetica.ru/jour/article/view/104

В обзоре рассмотрены особенности фармакокинетики лекарственных препаратов, содержащих морфолиновый цикл. Большое внимание уделено биотрансформации данных соединений. Дана краткая характеристика фармакологических эффектов морфолинсодержащих лекарственных препаратов.

биотрансформацияфармакокинетикаморфолиносодержащие лекарственные препаратыReferencesАдаскевич В. П. Противогрибковые лекарственные средства в дерматологии//Вестник фармации. 2007. № 2. С. 80-91.Адаскевич В. П. Противогрибковые лекарственные средства в дерматологии//Вестник фармации. 2007. № 2. С. 80-91.Аляутдин Р. Н. Фармакология. М.: ГЭОТАРМЕД, 2004. 592 с.Аляутдин Р. Н. Фармакология. М.: ГЭОТАРМЕД, 2004. 592 с.Асатрян Т. О, Маркарян Э. А., Арустамян Ж С., Аветисян С. В., Маркарян Р. Э., Маркарян К. Ж., Григорян А. В. Синтез и свойства N-ациламинопроизводных 1,6,7-замещенных 1,2,3,4-тетрагидроизохинолин-4 спироциклопентанов и некоторых их аналогов//Хим. фарм. журнал. 2006. № 7. С. 16-17.Асатрян Т. О, Маркарян Э. А., Арустамян Ж С., Аветисян С. В., Маркарян Р. Э., Маркарян К. Ж., Григорян А. В. Синтез и свойства N-ациламинопроизводных 1,6,7-замещенных 1,2,3,4-тетрагидроизохинолин-4 спироциклопентанов и некоторых их аналогов//Хим. фарм. журнал. 2006. № 7. С. 16-17.Байкенова Г. Г., Абдулина Г. А., Газалиев А. М., Фазылов С. Д., Кудайбергенова С. Ж. Синтез и антимикробная активность дитиокарбаматов анабазина, пиперидина и морфолина//Хим. фарм. журнал. 2004. № 1. С. 19-20.Байкенова Г. Г., Абдулина Г. А., Газалиев А. М., Фазылов С. Д., Кудайбергенова С. Ж. Синтез и антимикробная активность дитиокарбаматов анабазина, пиперидина и морфолина//Хим. фарм. журнал. 2004. № 1. С. 19-20.Виглинская А. О. Экспериментальное изучение фармакокинетики и метаболизма оригинального селективного анксиолитика афобазола. Дис.. канд. мед. наук. М., 2007. 123 с.Виглинская А. О. Экспериментальное изучение фармакокинетики и метаболизма оригинального селективного анксиолитика афобазола. Дис.. канд. мед. наук. М., 2007. 123 с.Вихляев Ю.И., Ульянова О.В., Воронина Т. А. Антикаталептическая активность производных 2-аминоадамантана//Хим. фарм. Журнал. 1980. № 5. С. 45-48.Вихляев Ю.И., Ульянова О.В., Воронина Т. А. Антикаталептическая активность производных 2-аминоадамантана//Хим. фарм. Журнал. 1980. № 5. С. 45-48.Гагаузов Й. Н.//Химия и индустрия. 1966. Т. 38, № 7. С. 314-317.Гагаузов Й. Н.//Химия и индустрия. 1966. Т. 38, № 7. С. 314-317.Козьминых В. О., Беляев А. О., Козьминых Е. Н., Махмудов Р. Р., Одегова Т. Ф. Синтез, противомикробная и анальгетическая активность 4-арил-2^-морфолино-4-оксо-2-бутеновых кислот//Хим.-фарм. журнал. 2004. № 8. С. 25-26.Козьминых В. О., Беляев А. О., Козьминых Е. Н., Махмудов Р. Р., Одегова Т. Ф. Синтез, противомикробная и анальгетическая активность 4-арил-2^-морфолино-4-оксо-2-бутеновых кислот//Хим.-фарм. журнал. 2004. № 8. С. 25-26.Козьминых В. О, Беляев А. О., Козьминых Е. Н., Махмудов Р. Р., Одегова Т. Ф. Синтез, противомикробная и анальгетическая активность 4-арил-2-трет-бутиламино-4-оксо-2-бутеновых кислот//Хим.-фарм. журнал. 2004. № 11. С. 19-21.Козьминых В. О, Беляев А. О., Козьминых Е. Н., Махмудов Р. Р., Одегова Т. Ф. Синтез, противомикробная и анальгетическая активность 4-арил-2-трет-бутиламино-4-оксо-2-бутеновых кислот//Хим.-фарм. журнал. 2004. № 11. С. 19-21.Коптева Н.И. Химия соединений с морфолиновым циклом. Воронеж: изд-во Воронеж. ун-та. 1991. 140 с.Коптева Н.И. Химия соединений с морфолиновым циклом. Воронеж: изд-во Воронеж. ун-та. 1991. 140 с.Крыжановский С.А., Сорокина А. В., Столярук В. Н., Вититнова М. Б., Мирошкина И.А., Цорин И. Б., Дурнев А.Д., Середенин С. Б. Изучение антиишемического действия «Афобазола» в условиях экспериментального инфаркта миокарда//Бюлл. экспер. биол. и мед. 2010. № 150. С. 284-287.Крыжановский С.А., Сорокина А. В., Столярук В. Н., Вититнова М. Б., Мирошкина И.А., Цорин И. Б., Дурнев А.Д., Середенин С. Б. Изучение антиишемического действия «Афобазола» в условиях экспериментального инфаркта миокарда//Бюлл. экспер. биол. и мед. 2010. № 150. С. 284-287.Кудрин А. Н., Воробьев В. Г. Аминокетоны. М., 1970. 327 с.Кудрин А. Н., Воробьев В. Г. Аминокетоны. М., 1970. 327 с.Лиманский Е. С., Михайловский А. Г., Сыропятов Б. Я., Вахрин М. И. Синтез амидов 2- (3,3,7-триметил-3,4-дигидроизохинолил-1) этановой кислоты и их влияние на артериальное давление//Хим.-фарм. журнал. 2009. № 1. С. 5-7.Лиманский Е. С., Михайловский А. Г., Сыропятов Б. Я., Вахрин М. И. Синтез амидов 2- (3,3,7-триметил-3,4-дигидроизохинолил-1) этановой кислоты и их влияние на артериальное давление//Хим.-фарм. журнал. 2009. № 1. С. 5-7.Молодцова В. И. и др.//Изв. АН ЛатвССР. Сер. хим. 1983. — № 1. — С. 3-13.Молодцова В. И. и др.//Изв. АН ЛатвССР. Сер. хим. 1983. — № 1. — С. 3-13.Середенин С. Б. и др. Фармакокинетика афобазола у крыс//Экспер. и клин. фармакол. 2007. Т. 70, № 2. С. 59-64.Середенин С. Б. и др. Фармакокинетика афобазола у крыс//Экспер. и клин. фармакол. 2007. Т. 70, № 2. С. 59-64.Столярук В. Н., Вититнова М. Б., Крыжановский С. А. Изучение эффектов афобазола на модели реперфузионных аритмий//Вестник РАМН. 2010. С. 41-45.Столярук В. Н., Вититнова М. Б., Крыжановский С. А. Изучение эффектов афобазола на модели реперфузионных аритмий//Вестник РАМН. 2010. С. 41-45.AHFS Drug Information. American Society of Health-System Pharmacists. 2001. P. 835-837.AHFS Drug Information. American Society of Health-System Pharmacists. 2001. P. 835-837.Akira TANAKA et al. Excretion and Distribution of Morpholine Salts in Rats//Journal of the Food Hygienic Society of Japan. 1978. № 19. P. 329-334.Akira TANAKA et al. Excretion and Distribution of Morpholine Salts in Rats//Journal of the Food Hygienic Society of Japan. 1978. № 19. P. 329-334.Amrein R. et al. Interactions of moclobemide with concomitantly administered medication: evidence from pharmacological and clinical stud-ies//Psychopharmacology (Berl.). 1992. Vol. 106, Suppl. P. S2431.Amrein R. et al. Interactions of moclobemide with concomitantly administered medication: evidence from pharmacological and clinical stud-ies//Psychopharmacology (Berl.). 1992. Vol. 106, Suppl. P. S2431.Andes D., van Ogtrop M. L., Peng J., Craig W. A. In vivo pharmacodynamics of a new oxazolidinone (linezolid)//Antimicrob Agents Che-mother. 2002. Vol. 46, № 11. P. 3484-3489.Andes D., van Ogtrop M. L., Peng J., Craig W. A. In vivo pharmacodynamics of a new oxazolidinone (linezolid)//Antimicrob Agents Che-mother. 2002. Vol. 46, № 11. P. 3484-3489.Andreoli V. et al. Reboxetine, a new noradrenaline selective antidepressant, is at least as effective as fluoxetine in the treatment of depression//J. Clin. Psychopharmacol. 2002. № 22. P. 393-399.Andreoli V. et al. Reboxetine, a new noradrenaline selective antidepressant, is at least as effective as fluoxetine in the treatment of depression//J. Clin. Psychopharmacol. 2002. № 22. P. 393-399.Ayrton A., Morgan P. Role of transport proteins in drug absorption, distribution and excretion//Xenobiotica. 2001. № 31. P. 469-497.Ayrton A., Morgan P. Role of transport proteins in drug absorption, distribution and excretion//Xenobiotica. 2001. № 31. P. 469-497.Baghai T. C., Volz H.-P., Möller H.-J. Drug treatment of depression in the 2000 s: an overview of achievements in the last 10 years and future possibilities//World J. Biol. Psychiatry. 2006. № 7. P. 198-222.Baghai T. C., Volz H.-P., Möller H.-J. Drug treatment of depression in the 2000 s: an overview of achievements in the last 10 years and future possibilities//World J. Biol. Psychiatry. 2006. № 7. P. 198-222.Baran R., Feulhade M., Datry A. et al. A randoomized trial of amorolfine 5 % solution nail laquer associated with oral terfinafine compared with terbi-nafine alone in the treatment of dermatophytic toenail onychomycoses affecting the matrix region//Br. J. Dermatol. 2000. 142. P. 1177-1183.Baran R., Feulhade M., Datry A. et al. A randoomized trial of amorolfine 5 % solution nail laquer associated with oral terfinafine compared with terbi-nafine alone in the treatment of dermatophytic toenail onychomycoses affecting the matrix region//Br. J. Dermatol. 2000. 142. P. 1177-1183.Bayliss P. F., Case D. E. Blood level studies with viloxazine hydrochloride in man//Br. J. Clin. Pharmacol. 1975. № 2. P. 209-214.Bayliss P. F., Case D. E. Blood level studies with viloxazine hydrochloride in man//Br. J. Clin. Pharmacol. 1975. № 2. P. 209-214.Bayliss P. F. C., Dewsbury A. R., Donald J. F. et al. A double blind controlled trial of ‘Vivalan’ (viloxazine hydrochloride) and imipramine hydrochloride in the treatment of depression in general practice//J. Int. Med. Res. 1974. № 2. P. 260-264.Bayliss P. F. C., Dewsbury A. R., Donald J. F. et al. A double blind controlled trial of ‘Vivalan’ (viloxazine hydrochloride) and imipramine hydrochloride in the treatment of depression in general practice//J. Int. Med. Res. 1974. № 2. P. 260-264.Benedek I. H., Davidson A. F., Pieniaszek H. J. Jr. Enzyme induction by moricizine: time course and extent in healthy subjects//J. Clin. Pharmacol. 1994. № 34. P. 167-175.Benedek I. H., Davidson A. F., Pieniaszek H. J. Jr. Enzyme induction by moricizine: time course and extent in healthy subjects//J. Clin. Pharmacol. 1994. № 34. P. 167-175.Bergstrand R. et al. Intravenous and oral administration of molsidomine, a pharmacodynamic and pharmacokinetic study//Eur. J. Clin. Pharmacol. 1984. № 27. P. 203-208.Bergstrand R. et al. Intravenous and oral administration of molsidomine, a pharmacodynamic and pharmacokinetic study//Eur. J. Clin. Pharmacol. 1984. № 27. P. 203-208.Berlin I. et al. Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects//Br. J. Clin. Pharmacol. 1990. № 30. P. 805-816.Berlin I. et al. Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects//Br. J. Clin. Pharmacol. 1990. № 30. P. 805-816.Butman S. M., Knoll M. L., Gardin J. M. Comparison ofethmozine to propranolol andthe combination forventricular arrhythmias//Am. J. Cardiol. 1987. Vol. 60, № 7. P. 603-607.Butman S. M., Knoll M. L., Gardin J. M. Comparison ofethmozine to propranolol andthe combination forventricular arrhythmias//Am. J. Cardiol. 1987. Vol. 60, № 7. P. 603-607.Case D. E., Reeves P. R. The Disposition and Metabolism of I. C.I. 58,834 (Viloxazine) in Humans//Xenobiotica. 1975. № 5. P. 113-129.Case D. E., Reeves P. R. The Disposition and Metabolism of I. C.I. 58,834 (Viloxazine) in Humans//Xenobiotica. 1975. № 5. P. 113-129.Case D. E. et al. The Disposition and Metabolism of LCI. 58,834 (ViloxazJne) in Animals//Xenobiotica. 1975. № 5. P. 83-111.Case D. E. et al. The Disposition and Metabolism of LCI. 58,834 (ViloxazJne) in Animals//Xenobiotica. 1975. № 5. P. 83-111.Clemett D., Markham A. Linezolid//Drugs. 2000. Vol. 59, № 4. P. 815-827.Clemett D., Markham A. Linezolid//Drugs. 2000. Vol. 59, № 4. P. 815-827.Cocchiara G. et al. Comparison of the disposition and of the metabolic pattern of Reboxetine, a new antidepressant, in the rat, dog, monkey and man//Eur. J. Drug. Metab. Pharmacokinet. 1991. № 16. P. 231-239.Cocchiara G. et al. Comparison of the disposition and of the metabolic pattern of Reboxetine, a new antidepressant, in the rat, dog, monkey and man//Eur. J. Drug. Metab. Pharmacokinet. 1991. № 16. P. 231-239.Cottagnoud P., Gerber C. M., Acosta F., Cottagnoud M., Neftel K., Tauber M. G. Linezolid against penicillin-sensitive and resistant pneumococci in the rabbit meningitis model//J. Antimicrob. Chemother. 2000. Vol. 46. № 6. P. 981-985.Cottagnoud P., Gerber C. M., Acosta F., Cottagnoud M., Neftel K., Tauber M. G. Linezolid against penicillin-sensitive and resistant pneumococci in the rabbit meningitis model//J. Antimicrob. Chemother. 2000. Vol. 46. № 6. P. 981-985.Coulomb F. et al. Pharmacokinetics of single-dose reboxetine in volunteers with renal insufficiency//J. Clin. Pharmacol. 2000. № 40. P. 482-487.Coulomb F. et al. Pharmacokinetics of single-dose reboxetine in volunteers with renal insufficiency//J. Clin. Pharmacol. 2000. № 40. P. 482-487.Dahl M. L., Bertilsson L. Genetically variable metabolism of antidepressants and neuroleptic drugs in man//Pharmacogenetics. 1993. № 3. P. 61-70.Dahl M. L., Bertilsson L. Genetically variable metabolism of antidepressants and neuroleptic drugs in man//Pharmacogenetics. 1993. № 3. P. 61-70.De Jongh D. K., Van Proosdij-Hartzema E. G. Pharmacology of (+)-, (+)-and (-)-2:2-diphenyl-3-methyl-4-morpholino-butyrylpyrrolidi-ne//J. Pharm. Pharmacol. 1957. № 9. P. 730-738.De Jongh D. K., Van Proosdij-Hartzema E. G. Pharmacology of (+)-, (+)-and (-)-2:2-diphenyl-3-methyl-4-morpholino-butyrylpyrrolidi-ne//J. Pharm. Pharmacol. 1957. № 9. P. 730-738.Dell D., Fromson J. M., Illing H. P. A. et al. Pharmacokinetics and pharmacodynamics of molsidomine in man//Br. J. Clin. Pharmacol. 1978. № 5. P. 395-360.Dell D., Fromson J. M., Illing H. P. A. et al. Pharmacokinetics and pharmacodynamics of molsidomine in man//Br. J. Clin. Pharmacol. 1978. № 5. P. 395-360.Denissen J. F. et al. The orally active renin inhibitor A-74273. In vivo and in vitro morpholine ring metabolism in rats, dogs, and humans//Drug Metab. Dispos. 1994. № 22. P. 880-888.Denissen J. F. et al. The orally active renin inhibitor A-74273. In vivo and in vitro morpholine ring metabolism in rats, dogs, and humans//Drug Metab. Dispos. 1994. № 22. P. 880-888.Dingemanse J. An update of recent moclobemide interaction data//Int. Clin. Psychopharmacol. 1993. Vol. 7, № 3-4. P. 167-180.Dingemanse J. An update of recent moclobemide interaction data//Int. Clin. Psychopharmacol. 1993. Vol. 7, № 3-4. P. 167-180.Dostert P., Benedetti M. S., Poggesi I. Review of the pharmacokinetics and metabolism of reboxetine, a selective noradrenaline reuptake inhibitor//Eur. Neuropsychopharmacol. 1997. № 7. Suppl 1. С. S23-35; discussion S71-73.Dostert P., Benedetti M. S., Poggesi I. Review of the pharmacokinetics and metabolism of reboxetine, a selective noradrenaline reuptake inhibitor//Eur. Neuropsychopharmacol. 1997. № 7. Suppl 1. С. S23-35; discussion S71-73.Fleishaker J. C. Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression//Clin. Pharmacokinet. 2000. Vol. 39. № 6. P. 413-427.Fleishaker J. C. Clinical pharmacokinetics of reboxetine, a selective norepinephrine reuptake inhibitor for the treatment of patients with depression//Clin. Pharmacokinet. 2000. Vol. 39. № 6. P. 413-427.French G. Safety and tolerability of linezolid//J. Antimicrob. Chemother. 2003. 51 Suppl 2: ii45-53.French G. Safety and tolerability of linezolid//J. Antimicrob. Chemother. 2003. 51 Suppl 2: ii45-53.Gomez-Flores A., Welsh O., Said-Fernandez S., Lozano-Garza G., Tavarez-Alejandro R. E., Vera — Cabrera L. In vitro and in vivo activities of antimicrobials against Nocardia brasiliensis//Antimicrob. Agents. Chemother. 2004. Vol. 48, № 3. P. 832-837.Gomez-Flores A., Welsh O., Said-Fernandez S., Lozano-Garza G., Tavarez-Alejandro R. E., Vera — Cabrera L. In vitro and in vivo activities of antimicrobials against Nocardia brasiliensis//Antimicrob. Agents. Chemother. 2004. Vol. 48, № 3. P. 832-837.Goodman&Gilman. The Pharmacological Basis of Therapeutics/Ed. Harman J. G., Lombard L. E. 2001. 10 th ed. P. 1260-1261, 1147.Goodman&Gilman. The Pharmacological Basis of Therapeutics/Ed. Harman J. G., Lombard L. E. 2001. 10 th ed. P. 1260-1261, 1147.Gram L. F. et al. Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2 D6, and CYP1A2: A panel study [ast]//Clin Pharmacol Ther. 1995. Vol. 57, № 6. P. 670-677.Gram L. F. et al. Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2 D6, and CYP1A2: A panel study [ast]//Clin Pharmacol Ther. 1995. Vol. 57, № 6. P. 670-677.Härtter S. et al. The role of cytochrome P450 2 D6 in the metabolism of moclobemide//Eur/Neuropsychopharmacol. 1996. № 6. P. 225-230.Härtter S. et al. The role of cytochrome P450 2 D6 in the metabolism of moclobemide//Eur/Neuropsychopharmacol. 1996. № 6. P. 225-230.Hayashi T. Metabolism of 4-ethoxy-2-methyl-5-morpholino-3 (2 H)-pyridazinone (emorfazone). Effect of inducer pretreatment on oxygenation of the morpholino moiety in guinea pigs//Chem. Pharm. Bull. 1982. № 30. P. 3748-3756.Hayashi T. Metabolism of 4-ethoxy-2-methyl-5-morpholino-3 (2 H)-pyridazinone (emorfazone). Effect of inducer pretreatment on oxygenation of the morpholino moiety in guinea pigs//Chem. Pharm. Bull. 1982. № 30. P. 3748-3756.Hayes A. G., Chang T. Determination of indeloxazine, a new antidepressant agent, in human plasma by gas-liquid chromatography with elec-tron-capture detection//Journal of Chromatography. 1983. № 272. P. 176-180.Hayes A. G., Chang T. Determination of indeloxazine, a new antidepressant agent, in human plasma by gas-liquid chromatography with elec-tron-capture detection//Journal of Chromatography. 1983. № 272. P. 176-180.Herman B. D., Fleishaker J. C., Brown M. T. Ketoconazole inhibits the clearance of the enantiomers of the antidepressant reboxetine in hu-mans//Clin. Pharmacol. Ther. 1999. № 66. P. 374-379.Herman B. D., Fleishaker J. C., Brown M. T. Ketoconazole inhibits the clearance of the enantiomers of the antidepressant reboxetine in hu-mans//Clin. Pharmacol. Ther. 1999. № 66. P. 374-379.Howrie D.L. et al. Disposition of moracizine (ethmozine) in healthy subjects after oral administration of radiolabelled drug//Eur. J. Clin. Pharmacol. 1987. № 32. P. 607-610.Howrie D.L. et al. Disposition of moracizine (ethmozine) in healthy subjects after oral administration of radiolabelled drug//Eur. J. Clin. Pharmacol. 1987. № 32. P. 607-610.Huber T. et al. Pharmacokinetics and pharmacodynamics of molsidomine in patients with liver dysfunction due to congestive heart fail-ure//Int. J. Clin. Pharmacol. Ther. Toxicol. 1992. № 30. P. 491-492.Huber T. et al. Pharmacokinetics and pharmacodynamics of molsidomine in patients with liver dysfunction due to congestive heart fail-ure//Int. J. Clin. Pharmacol. Ther. Toxicol. 1992. № 30. P. 491-492.Humphrey S. J. et al. Cardiovascular sympathomimetic amine interactions in rats treated with monoamine oxidase inhibitors and the novel oxazolidinone antibiotic linezolid//J. Cardiovasc. Pharmacol. 2001. № 37. P. 548-563.Humphrey S. J. et al. Cardiovascular sympathomimetic amine interactions in rats treated with monoamine oxidase inhibitors and the novel oxazolidinone antibiotic linezolid//J. Cardiovasc. Pharmacol. 2001. № 37. P. 548-563.Jauch R. et al. Biotransformation of moclobemide in humans//Acta Psychiatr. Scand. Suppl. 1990. Vol. 360. P. 87-90Jauch R. et al. Biotransformation of moclobemide in humans//Acta Psychiatr. Scand. Suppl. 1990. Vol. 360. P. 87-90Jannuzzo M. G. et al. Effect of reboxetine on the pharmacokinetics of lorazepam in healthy volunteers//European Neuropsychopharmacology. 1995. № 5. P. 300-301.Jannuzzo M. G. et al. Effect of reboxetine on the pharmacokinetics of lorazepam in healthy volunteers//European Neuropsychopharmacology. 1995. № 5. P. 300-301.Kamimura H. et al. Disposition and metabolism of indeloxazine hydrochloride, a cerebral activator, in rats//Xenobiotica. 1987. № 17. P. 645-658.Kamimura H. et al. Disposition and metabolism of indeloxazine hydrochloride, a cerebral activator, in rats//Xenobiotica. 1987. № 17. P. 645-658.Kojima T., Niigata K., Fujikura T. et al. Syntheses of (/-)-2- [(inden-7-yloxy)methyl]morpholine hydrochloride (YM-08054, indeloxazine hydrochloride) and its derivatives with potential cerebral-activating and antidepressive properties//Chemical & Pharmaceutical Bulletin. 1985. № 33. P. 3766-3774.Kojima T., Niigata K., Fujikura T. et al. Syntheses of (/-)-2- [(inden-7-yloxy)methyl]morpholine hydrochloride (YM-08054, indeloxazine hydrochloride) and its derivatives with potential cerebral-activating and antidepressive properties//Chemical & Pharmaceutical Bulletin. 1985. № 33. P. 3766-3774.Korn A. et al. Effect of moclobemide, a new reversible monoamine oxidase inhibitor, on absorption and pressor effect oftyramine//J. Cardiovasc. Pharmacol. 1988. № 11. P. 17-23.Korn A. et al. Effect of moclobemide, a new reversible monoamine oxidase inhibitor, on absorption and pressor effect oftyramine//J. Cardiovasc. Pharmacol. 1988. № 11. P. 17-23.Kyriakopoulos A. A, Greenblatt D. J., Shader R. I. Clinical pharmacokinetics oflorazepam: a review//J. Clin. Psychiatry. 1978. № 39. P. 16-23.Kyriakopoulos A. A, Greenblatt D. J., Shader R. I. Clinical pharmacokinetics oflorazepam: a review//J. Clin. Psychiatry. 1978. № 39. P. 16-23.Laaban J. P., Dupeyron J. P., Lafay M., Sofeir M., Rochemaure J., Fabiani P. Theophylline intoxication following viloxazine induced decrease in clearance//European Journal of Clinical Pharmacology. 1986. № 30. P. 351-353.Laaban J. P., Dupeyron J. P., Lafay M., Sofeir M., Rochemaure J., Fabiani P. Theophylline intoxication following viloxazine induced decrease in clearance//European Journal of Clinical Pharmacology. 1986. № 30. P. 351-353.Leblanc B. et al. Binding of drugs to eye melanin is not predictive of ocular toxicity//Regul. Toxicol. Pharmacol. 1998. № 28. P. 124-132.Leblanc B. et al. Binding of drugs to eye melanin is not predictive of ocular toxicity//Regul. Toxicol. Pharmacol. 1998. № 28. P. 124-132.Leikin J. B., Paloucek F. P. Poisoning and toxicology handbook//Informa Health Care. 2007. Ed. 4 th. 1331 p.Leikin J. B., Paloucek F. P. Poisoning and toxicology handbook//Informa Health Care. 2007. Ed. 4 th. 1331 p.Li J. et al. Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes//Clin. Cancer Res. 2007. № 13. P. 3731-3737.Li J. et al. Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes//Clin. Cancer Res. 2007. № 13. P. 3731-3737.MacGowan A. P. Pharmacokinetic and pharmacodynamic profile of linezolid in healthy volunteers and patients with Gram-positive infec-tions//Journal ofAntimicrobial Chemotherapy. 2003. № 51. P. 17 ii-25.MacGowan A. P. Pharmacokinetic and pharmacodynamic profile of linezolid in healthy volunteers and patients with Gram-positive infec-tions//Journal ofAntimicrobial Chemotherapy. 2003. № 51. P. 17 ii-25.Maguire K., Pereira A., Tiller J. Moclobemide pharmacokinetics in depressed patients: Lack of age effect//Human Psychopharmacology: Clinical and Experimental. 1991. № 6. P. 249-252.Maguire K., Pereira A., Tiller J. Moclobemide pharmacokinetics in depressed patients: Lack of age effect//Human Psychopharmacology: Clinical and Experimental. 1991. № 6. P. 249-252.Martindale Extra Pharmacopeeia. Royal Pharmaceutical Society/Ed JEF Reynolds 36 th Edition. 2009. P. 293-95.Martindale Extra Pharmacopeeia. Royal Pharmaceutical Society/Ed JEF Reynolds 36 th Edition. 2009. P. 293-95.McKillop D. et al. In vitro metabolism of gefitinib in human liver microsomes//Xenobiotica. 2004. № 34. P. 983-1000.McKillop D. et al. In vitro metabolism of gefitinib in human liver microsomes//Xenobiotica. 2004. № 34. P. 983-1000.McKillop D. et al. Metabolic disposition of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in rat, dog and man//Xenobiotica. 2004. № 34. P. 917-934.McKillop D. et al. Metabolic disposition of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in rat, dog and man//Xenobiotica. 2004. № 34. P. 917-934.Mckillop D. et al. Cytochrome P450-dependent metabolism of gefitinib//Xenobiotica. 2005. № 35. P. 39-50.Mckillop D. et al. Cytochrome P450-dependent metabolism of gefitinib//Xenobiotica. 2005. № 35. P. 39-50.McKillop D. et al. Pharmacokinetics of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in rat and dog//Xenobiotica. 2004. Vol. 34, № 10. P. 901-915.McKillop D. et al. Pharmacokinetics of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, in rat and dog//Xenobiotica. 2004. Vol. 34, № 10. P. 901-915.Montellano P. R. O. Cytochrome P450: structure, mechanism, and biochemistry//Free Radical Biology & Medicine. 1996. № 21. P. 251.Montellano P. R. O. Cytochrome P450: structure, mechanism, and biochemistry//Free Radical Biology & Medicine. 1996. № 21. P. 251.Nakamura Y. et al. Pharmacokinetics of gefitinib predicts antitumor activity for advanced non-small cell lung cancer//J. Thorac. Oncol. 2010. № 5. P. 1404-1409.Nakamura Y. et al. Pharmacokinetics of gefitinib predicts antitumor activity for advanced non-small cell lung cancer//J. Thorac. Oncol. 2010. № 5. P. 1404-1409.Ogawa N., Haba K., Sora Y. H., Higashida A., Sato H., Ogawa S. Comparison of the effects ofbifemelane hydrochloride and indeloxazine hydrochloride on scopolamine hydrobromide-induced impairment in radial maze performance//Clinical Therapeutics. 1988. № 10. P. 704-711.Ogawa N., Haba K., Sora Y. H., Higashida A., Sato H., Ogawa S. Comparison of the effects ofbifemelane hydrochloride and indeloxazine hydrochloride on scopolamine hydrobromide-induced impairment in radial maze performance//Clinical Therapeutics. 1988. № 10. P. 704-711.Ostrowski J., Resag K. Pharmacokinetics of molsidomine in humans//Am. Heart J. 1985. № 109. P. 641-643.Ostrowski J., Resag K. Pharmacokinetics of molsidomine in humans//Am. Heart J. 1985. № 109. P. 641-643.Ostrowski J., Schweizer P., Erbel R. et al. Correlation of pharmacokinetic data to clinical effect of molsidomine//Proceedings of the First European Congress on Biopharmacology and Pharmacokinetics: 1981 Apr 1-3; Clermont Ferrand 1981; 3: P. 418-424.Ostrowski J., Schweizer P., Erbel R. et al. Correlation of pharmacokinetic data to clinical effect of molsidomine//Proceedings of the First European Congress on Biopharmacology and Pharmacokinetics: 1981 Apr 1-3; Clermont Ferrand 1981; 3: P. 418-424.Peet M. A clinical trial of ICI 58,834-a potential antidepressant//J. Int. Med. Res. 1973. № 1. P. 624-626.Peet M. A clinical trial of ICI 58,834-a potential antidepressant//J. Int. Med. Res. 1973. № 1. P. 624-626.Perault M. C., Griesemann E., Bouquet S., Lavoisy J., Vandel B. A study of the interaction of viloxazine with theophylline//Therapeutic Drug Monitoring. 1989. № 11. P. 520-522.Perault M. C., Griesemann E., Bouquet S., Lavoisy J., Vandel B. A study of the interaction of viloxazine with theophylline//Therapeutic Drug Monitoring. 1989. № 11. P. 520-522.Pfizer ZYVOX (linezolid) Label Information (PDF) (June 20, 2008).Pfizer ZYVOX (linezolid) Label Information (PDF) (June 20, 2008).Pieniaszek H. J. Jr et al. Human moricizine metabolism. II. Quantification and pharmacokinetics of plasma and urinary metabolites//Xeno-biotica. 1999. Vol. 29, № 9. P. 945-955.Pieniaszek H. J. Jr et al. Human moricizine metabolism. II. Quantification and pharmacokinetics of plasma and urinary metabolites//Xeno-biotica. 1999. Vol. 29, № 9. P. 945-955.Pieniaszek H. J. Jr et al. Influence of food on the oral absorption and bioavailability of moricizine//J. Clin. Pharmacol. 1991. № 31. P. 792-795.Pieniaszek H. J. Jr et al. Influence of food on the oral absorption and bioavailability of moricizine//J. Clin. Pharmacol. 1991. № 31. P. 792-795.Pinder R. M. et al. Viloxazine: a review of its pharmacological properties and therapeutic efficacy in depressive illness//Drugs. 1977. № 13. P.401-421Pinder R. M. et al. Viloxazine: a review of its pharmacological properties and therapeutic efficacy in depressive illness//Drugs. 1977. № 13. P.401-421Pisani F. F. A., Pisani F., Fazio A., Artesi C. et al. Elevation of plasma phenytoin by viloxazine in epileptic patients: a clinically significant drug interaction//Journal of Neurology, Neurosurgery, and Psychiatry. 1992. № 55. P. 126-127.Pisani F. F. A., Pisani F., Fazio A., Artesi C. et al. Elevation of plasma phenytoin by viloxazine in epileptic patients: a clinically significant drug interaction//Journal of Neurology, Neurosurgery, and Psychiatry. 1992. № 55. P. 126-127.Pitts J. E., Bruce R. B., Forehand J. B. Identification of doxapram metabolites using high pressure ion exchange chromatography and mass spectroscopy//Xenobiotica. 1973. № 3. P. 73-83.Pitts J. E., Bruce R. B., Forehand J. B. Identification of doxapram metabolites using high pressure ion exchange chromatography and mass spectroscopy//Xenobiotica. 1973. № 3. P. 73-83.PoggesiI., Pellizzoni C., Fleishaker J. C. Pharmacokinetics of reboxetine in elderly patients with depressive disorders//Int. J. Clin. Pharmacol. Ther. 2000. № 38. P. 254-259.PoggesiI., Pellizzoni C., Fleishaker J. C. Pharmacokinetics of reboxetine in elderly patients with depressive disorders//Int. J. Clin. Pharmacol. Ther. 2000. № 38. P. 254-259.Pons G. et al. Moclobemide excretion in human breast milk//Br. J. Clin. Pharmacol. 1990. № 29. P. 27-31.Pons G. et al. Moclobemide excretion in human breast milk//Br. J. Clin. Pharmacol. 1990. № 29. P. 27-31.Pratt C. M. et al. Antiarrhythmic efficacy of Ethmozine (moricizine HCl) compared with disopyramide and propranolol//Am. J. Cardiol. 1987. Vol. 60, № 11. P. 52 F-58 F.Pratt C. M. et al. Antiarrhythmic efficacy of Ethmozine (moricizine HCl) compared with disopyramide and propranolol//Am. J. Cardiol. 1987. Vol. 60, № 11. P. 52 F-58 F.Richards L. E. et al. Human moricizine metabolism. I. Isolation and identification of metabolites in human urine//Xenobiotica. 1997. № 27. P. 217-229.Richards L. E. et al. Human moricizine metabolism. I. Isolation and identification of metabolites in human urine//Xenobiotica. 1997. № 27. P. 217-229.Rocchetti M., Pellizzoni C., Poggesi I., Davies D. S., Wilkins M. R., Hirokawa K., Dostert P. and Benedetti M. S. Genetic polymorphism and reboxetine metabolism//1 st Congress of the European Association for Clinical Pharmacology and Therapeutics. Therapie (Suppl). 1995. Abstract No. 80.Rocchetti M., Pellizzoni C., Poggesi I., Davies D. S., Wilkins M. R., Hirokawa K., Dostert P. and Benedetti M. S. Genetic polymorphism and reboxetine metabolism//1 st Congress of the European Association for Clinical Pharmacology and Therapeutics. Therapie (Suppl). 1995. Abstract No. 80.Rosenkranz B., Winkelmann B. R., Parnham M. J. Clinical pharmacokinetics of molsidomine//Clin. Pharmacokinet. 1996. № 30. P. 372-384.Rosenkranz B., Winkelmann B. R., Parnham M. J. Clinical pharmacokinetics of molsidomine//Clin. Pharmacokinet. 1996. № 30. P. 372-384.Schoerlin M. P. et al. Cimetidine alters the disposition kinetics of the monoamine oxidase-A inhibitor moclobemide//Clin. Pharmacol. Ther. 1991. Vol. 49, № 1. P. 32-38.Schoerlin M. P. et al. Cimetidine alters the disposition kinetics of the monoamine oxidase-A inhibitor moclobemide//Clin. Pharmacol. Ther. 1991. Vol. 49, № 1. P. 32-38.Setoguchi M. et al. Pharmacological studies on Y-8894 (VI). The effect on monoamine uptake and turnover in mouse brain//Nippon Yakurigaku Zasshi. 1987. № 90. P. 41-49.Setoguchi M. et al. Pharmacological studies on Y-8894 (VI). The effect on monoamine uptake and turnover in mouse brain//Nippon Yakurigaku Zasshi. 1987. № 90. P. 41-49.Sheldon R. S. et al. Aminoalkyl structural requirements for interaction of lidocaine with the class I antiarrhythmic drug receptor on rat cardiac myocytes//Mol. Pharmacol. 1991. № 39. P. 609-614.Sheldon R. S. et al. Aminoalkyl structural requirements for interaction of lidocaine with the class I antiarrhythmic drug receptor on rat cardiac myocytes//Mol. Pharmacol. 1991. № 39. P. 609-614.Siddoway L. A. et al. Clinical pharmacokinetics of moricizine//Am. J. Cardiol. 1990. Vol. 65, № 8. P. 21 D-25 D.Siddoway L. A. et al. Clinical pharmacokinetics of moricizine//Am. J. Cardiol. 1990. Vol. 65, № 8. P. 21 D-25 D.Slatter J. G. et al. Pharmacokinetics, toxicokinetics, distribution, metabolism and excretion of linezolid in mouse, rat and dog//Xenobiotica. 2002. № 32. P. 907-924.Slatter J. G. et al. Pharmacokinetics, toxicokinetics, distribution, metabolism and excretion of linezolid in mouse, rat and dog//Xenobiotica. 2002. № 32. P. 907-924.Spreux-Varoquaux O. et al. Pharmacokinetics of molsidomine and of its active metabolite, SIN-1 (or linsidomine), in the elderly//Fundam Clin Pharmacol. 1991. № 5. P. 549-556.Spreux-Varoquaux O. et al. Pharmacokinetics of molsidomine and of its active metabolite, SIN-1 (or linsidomine), in the elderly//Fundam Clin Pharmacol. 1991. № 5. P. 549-556.Stalker D. J., Jungbluth G. L. Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial//Clin. Pharmacokinet. 2003. Vol. 42, № 13. P. 1129-1140.Stalker D. J., Jungbluth G. L. Clinical pharmacokinetics of linezolid, a novel oxazolidinone antibacterial//Clin. Pharmacokinet. 2003. Vol. 42, № 13. P. 1129-1140.Stern E. S., Wood D. R.//J. Pharmac. Pharmacol. 1959. P. 140-142.Stern E. S., Wood D. R.//J. Pharmac. Pharmacol. 1959. P. 140-142.Stoeckel K. et al. Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function//Acta Psychi-atr. Scand. Suppl. 1990. № 360. P. 94-97.Stoeckel K. et al. Absorption and disposition of moclobemide in patients with advanced age or reduced liver or kidney function//Acta Psychi-atr. Scand. Suppl. 1990. № 360. P. 94-97.Strasser R., Klepzig H., Ostrowski J. et al. Molsidomin bei koronarer Herzkrankheit//Munch. Med. Wochenschr. 1983. Vol. 125. P. 156-158.Strasser R., Klepzig H., Ostrowski J. et al. Molsidomin bei koronarer Herzkrankheit//Munch. Med. Wochenschr. 1983. Vol. 125. P. 156-158.Swaisland H. C. et al. Pharmacokinetic drug interactions ofgefitinib with rifampicin, itraconazole and metoprolol//Clin. Pharmacokinet. 2005. Vol. 44, № 10. P. 1067-1081.Swaisland H. C. et al. Pharmacokinetic drug interactions ofgefitinib with rifampicin, itraconazole and metoprolol//Clin. Pharmacokinet. 2005. Vol. 44, № 10. P. 1067-1081.The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9 th ed. Boston, Mass: Little, Brown & Co., 1994. P. 253-256.The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9 th ed. Boston, Mass: Little, Brown & Co., 1994. P. 253-256.Tocco D. J. et al. Timolol metabolism in man and laboratory animals//Drug Metab. Dispos. 1980. № 8. P. 236-240.Tocco D. J. et al. Timolol metabolism in man and laboratory animals//Drug Metab. Dispos. 1980. № 8. P. 236-240.Tsegos I. K., EkdawiM. Y. A double blind controlled study of viloxazine and imipramine in depression//Curr. Med. Res. Opin. 1974. № 2. P. 455-460.Tsegos I. K., EkdawiM. Y. A double blind controlled study of viloxazine and imipramine in depression//Curr. Med. Res. Opin. 1974. № 2. P. 455-460.Tyrer P. Towards rational therapy with monoamine oxidase inhibitors//Br. J. Psychiatry. 1976. № 128. P. 354-360.Tyrer P. Towards rational therapy with monoamine oxidase inhibitors//Br. J. Psychiatry. 1976. № 128. P. 354-360.Vaughan Williams E. M. Classifying antiarrhythmic actions: by facts or speculation//J. Clin. Pharmacol. 1992. № 32. P. 964-977.Vaughan Williams E. M. Classifying antiarrhythmic actions: by facts or speculation//J. Clin. Pharmacol. 1992. № 32. P. 964-977.Weiser J. R., Heger K. H., Oltmanns D. et al. Zur Pharmakokinetik von Molsidomin bei eingeschrankter Leberfunktion//Herzmedizin. 1986. № 9. P. 41-46.Weiser J. R., Heger K. H., Oltmanns D. et al. Zur Pharmakokinetik von Molsidomin bei eingeschrankter Leberfunktion//Herzmedizin. 1986. № 9. P. 41-46.Whitehouse T. et al. Pharmacokinetic studies of linezolid and teicoplanin in the critically ill//J. Antimicrob. Chemother. 2005. № 55. P. 333-340.Whitehouse T. et al. Pharmacokinetic studies of linezolid and teicoplanin in the critically ill//J. Antimicrob. Chemother. 2005. № 55. P. 333-340.Wienkers A. C., Wienkers L. C., Allievi C., Hauer M. J., Wynalda M. A. Cytochrome P-450-Mediated Metabolism of the Individual Enantio-mers of the Antidepressant Agent Reboxetine in Human Liver Microsomes//Drug Metabolism & Disposition. 1999. № 27. P. 1334-1340.Wienkers A. C., Wienkers L. C., Allievi C., Hauer M. J., Wynalda M. A. Cytochrome P-450-Mediated Metabolism of the Individual Enantio-mers of the Antidepressant Agent Reboxetine in Human Liver Microsomes//Drug Metabolism & Disposition. 1999. № 27. P. 1334-1340.Wiesel F. A., Raaflaub J., Kettler R. Pharmacokinetics of oral moclobemide in healthy human subjects and effects on MAO-activity in platelets and excretion of urine monoamine metabolites//Eur. J. Clin. Pharmacol. 1985. № 28. P. 89-95.Wiesel F. A., Raaflaub J., Kettler R. Pharmacokinetics of oral moclobemide in healthy human subjects and effects on MAO-activity in platelets and excretion of urine monoamine metabolites//Eur. J. Clin. Pharmacol. 1985. № 28. P. 89-95.Wildgrube H. J. et al. Liver function and pharmacokinetics of molsidomine and its metabolite 3-morpholinosydnonimine in healthy volun-teers//Arzneimittelforschung. 1986. Vol. 36, № 7. P. 1129-1133.Wildgrube H. J. et al. Liver function and pharmacokinetics of molsidomine and its metabolite 3-morpholinosydnonimine in healthy volun-teers//Arzneimittelforschung. 1986. Vol. 36, № 7. P. 1129-1133.Wilson I. D. et al. The metabolism of [14 C]N-ethoxycarbonyl-3-morpholinosydnonimine (molsidomine) in laboratory animals//Xenobi-otica. 1986. Vol. 16, № 12. P. 1117-1128.Wilson I. D. et al. The metabolism of [14 C]N-ethoxycarbonyl-3-morpholinosydnonimine (molsidomine) in laboratory animals//Xenobi-otica. 1986. Vol. 16, № 12. P. 1117-1128.Woosley R. L. et al. Pharmacokinetics of moricizine HCl//Am. J. Cardiol. 1987. № 60. P. 35 F-39 F.Woosley R. L. et al. Pharmacokinetics of moricizine HCl//Am. J. Cardiol. 1987. № 60. P. 35 F-39 F.Wynalda M. A., Hauer M. J., Wienkers L. C. Oxidation of the novel oxazolidinone antibiotic linezolid in human liver microsomes//Drug Metab. Dispos. 2000. № 28. P. 1014-1017.Wynalda M. A., Hauer M. J., Wienkers L. C. Oxidation of the novel oxazolidinone antibiotic linezolid in human liver microsomes//Drug Metab. Dispos. 2000. № 28. P. 1014-1017.Yamamoto M. O. M., Yamamoto M., Ooyama M., Ozawa Y. et al. Effects of indeloxazine hydrochloride, a cerebral activator, on passive avoidance learning impaired by disruption of cholinergic transmission in rats//Neuropharmacology. 1993. № 32. P. 695-701.Yamamoto M. O. M., Yamamoto M., Ooyama M., Ozawa Y. et al. Effects of indeloxazine hydrochloride, a cerebral activator, on passive avoidance learning impaired by disruption of cholinergic transmission in rats//Neuropharmacology. 1993. № 32. P. 695-701.Zimmer R., Fischbach R., Breuel H. P. Potentiation of the pressor effect of intravenously administered tyramine during moclobemide treat-ment//Acta Psychiatr. Scand. Suppl. 1990. № 360. P. 76-77.Zimmer R., Fischbach R., Breuel H. P. Potentiation of the pressor effect of intravenously administered tyramine during moclobemide treat-ment//Acta Psychiatr. Scand. Suppl. 1990. № 360. P. 76-77.Zimmer R. et al. Interaction studies with moclobemide//Acta Psychiatr. Scand. Suppl. 1990. № 360. P. 84-86.Zimmer R. et al. Interaction studies with moclobemide//Acta Psychiatr. Scand. Suppl. 1990. № 360. P. 84-86.

The authors declare that there are no conflicts of interest present.