Pharmacokinetic and safety comparison of two dosage strengths of the drug Ranquilon®: a bioequivalence study

Aim. To evaluate the comparative pharmacokinetics, bioequivalence, and safety of the test product Ranquilon® 2 mg tablets and the reference drug Ranquilon®1 mg tablets in healthy volunteers under fed conditions.

Material and methods. A randomized, open-label, comparative, two-period crossover study was conducted to evaluate the pharmacokinetic parameters, bioequivalence, and safety of two dosage strengths of the drug Ranquilon® — 1 mg tablets and 2 mg tablets. Thirty-six healthy volunteers were randomized into two sequence groups (n =18 per group). Participants in group 1 (sequence RT) received two 1 mg tablets of Ranquilon® in period 1 and one 2 mg tablet of Ranquilon® in period 2. Participants in group 2 (sequence TR) received the study drugs in the reverse order. The washout period between dosing was 7 days. The plasma concentration of the active substance of Ranquilon® (amide N-(6-phenylhexanoyl)glycyl-L-tryptophan) was determined using a validated method of high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS). Vital sings, clinical laboratory parameters (complete blood count and biochemical blood analysis, urinalysis), and 12-lead electrocardiogram (ECG) data were monitored and evaluated during the study. All subjectreported complaints, as well as any deviations from reference ranges in volunteers’ clinical condition, laboratory tests results, and ECG parameters, were considered by the investigators as adverse events (AEs).

Results. The mean maximum plasma concentration (C_max) was 8.00±3.67 ng/ml for the test product and 8.29±3.75 ng/ml for the reference drug. The mean area under the concentration-time curve (AUC_0-t) was 18.91±7.49 ng × hr/ml for the test product, and 21.05±8.33 for the reference drug. The calculated 90 % confidence intervals (CI) for the mean ratios (test/reference) of C_max and AUC_0-t were 83.36–107.74 % and 83.06–98.61 %, respectively. Both intervals fall within the predefined bioequivalence range of 80.00–125.00 %. A total of 22 adverse events (AEs) were reported in 13 volunteers. Eight AEs occurred in 5 volunteers (27.8 %) in group 1, and fourteen AEs in 8 volunteers (44.4 %) in group 2. All AEs were mild in severity, resolved spontaneously without sequelae, and required no therapeutic intervention or study-drug discontinuation.

Conclusion. Bioequivalence between the test product Ranquilon® 2 mg tablets and the reference drug Ranquilon® 1 mg tablets was conclusively demonstrated at an equivalent dose of 2 mg of the active substance. Both products exhibited favorable and comparable safety profiles.

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