Pharmacokinetics and Bioequivalence Study of the Two 20-MG Quinapril Hydrochloride Tablet Formulations in Healthy Thai Male Volunteers
Noppamas Rojanasthien MD*, Nayada Nasangiam MS*, Boonyium Kumsorn MS*, Sukit Roongapinun MD*, Apiwat Jengjareon MD*
Affiliation : * Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai
Objective : To determine the pharmacokinetics and bioequivalence of two 20-mg quinapril hydrochloride
tablet preparations; Quinaril® (The Biolab Ltd, Bangkok, Thailand) as the test and Accupril® as the reference.
Material and Method: The present study was a single dose, randomized, two-period crossover design conducted
in 24 healthy volunteers under fasting conditions with a 7-day washout period. Serial plasma concentrations
of quinapril and its active metabolite quinaprilat up to 24 h after dosing were determined by HPLC with UV
detection. The pharmacokinetic parameters were analyzed by noncompartmental analysis and the ANOVA
was carried out using logarithmically transformed data of the AUC and Cmax as well as untransformed Tmax.
Results : There were no significant differences between the two preparations regarding the Tmax of quinapril
and quinaprilat and their median Tmax were 0.5 h and 1.4 - 1.5 h, respectively. The half-life of quinapril (1.2 h)
was faster than quinaprilat (1.8-1.9 h) although the volume of distribution (Vd/F) of quinapril (1.1 L/kg) was
larger than quinaprilat (0.3 L/kg), however, its clearance rate (CL/F) was faster when compared to quinaprilat
(20-26 ml/min/kg vs. 1.7 ml/min/kg). The mean (90% CI) for the ratios Reference of quinapril were 0.99 (0.89-
1.10), 0.99 (0.90-1.09) and 1.01 (0.90-1.14), respectively for AUC0-24, AUC0-∞
and Cmax. Similarly, the corre-
sponding values for quinaprilat were 0.95 (0.90-1.01), 0.95 (0.90-1.01) and 1.03 (1.00-1.07), respectively.
These values were within the bioequivalence range of 0.80 - 1.25, thus, demonstrated the bioequivalence of
the two preparations.
Conclusion : The results of the present study indicated that the two quinapril HCL preparations are
bioequivalent and it can be assumed that they are therapeutically equivalent and exchangeable in clinical
practice.
Test
Keywords : Pharmacokinetics, Bioequivalence, Quinapril
