Evaluation of Ranquilon® pharmacokinetics, safety profile and tolerability in healthy volunteers: a phase I clinical trial.

Aim

Comparative evaluation of the pharmacokinetics, safety profile and tolerability of Ranquilon® 1 mg tablets with a single administration under fasting and fed conditions among healthy male and female volunteers.

Material and methods

In the open, prospective, randomized, three-period, crossover study, pharmacokinetics of the Ranquilon® 1-mg tablets was studied with three sequential doses of 3 mg (3 tablets) under fasting and fed conditions in 26 healthy female and male volunteers. In each study period, 16 blood samples were taken immediately before and within 10 hours after study drug administration. Quantitative determination of active ingredient of Ranquilon® in blood plasma samples was performed with high performance liquid chromatography-tandem mass-spectrometry method. The effect of food intake on the Ranquilon® pharmacokinetics was evaluated using the bioequivalence parameters AUC(0-t) and Cmax obtained before and after food intake. We also assessed safety profile and tolerability of Ranquilon®.

Results

The impact of food intake on the study drug AUC(0-t) was statistically significant, since its geometric mean ratio under fasting and fed conditions was 81.75% (90% CI 74.25–90.01%), which is beyond the 90% CI of 80.00–125.00%. However, food intake had no impact on Cmax, since its geometric mean ratio under fasting and fed conditions was 89.77% (90% CI: 81.82–98.5%) and fitted completely into the 80.00–125.00% interval. The average values of AUC(0-t) after a single dose of Ranquilon® in healthy volunteers under fasting and fed conditions were 17.502±8.587 ng×h/mL and 21.971±13.015 ng×h/mL, respectively. Therefore, the AUC(0-t) value increases by 1.26 times after Ranquilon® administration under fed condition compared with the fasting condition. During the study, one adverse event was reported in one volunteer (headache).

Conclusion

Our findings suggest that Ranquilon® 1 mg tablets should be taken during or after meals given its bioavailability and safety profile.

Key words

N-(6-phenylhexanoyl)glycyl-L-tryptophan, Ranquilon®, pharmacokinetics, food intake, healthy volunteers, safety, tolerability