Pharmacokinetics and bioequivalence study of the two 20-mg quinapril hydrochloride tablet formulations in healthy Thai male volunteers.
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.


METHODS
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 C as well as untransformed T(max).


RESULTS
There were no significant differences between the two preparations regarding the T(max) of quinapril and quinaprilat and their median T(max) 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/Test of quinapril were 0.99 (0.89-1.10), 0.99 (0.90-1.09) and 1.01 (0.90-1.14), respectively for AUC(0-24), AUC(0-infinity) and C(max). Similarly, the corresponding 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.


CONCLUSIONS
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.
Rojanasthien
Noppamas
N
Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. nrojanas@mail.med.cmu.ac.th
Nasangiam
Nayada
N
Kumsorn
Boonyium
B
Roongapinun
Sukit
S
Jengjareon
Apiwat
A
D000328:Adult; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D018592:Cross-Over Studies; D064368:Healthy Volunteers; D006801:Humans; D016014:Linear Models; D008297:Male; D000077583:Quinapril; D013607:Tablets; D044005:Tetrahydroisoquinolines / Q000493:pharmacokinetics* / Q000494:pharmacology; D013785:Thailand; D013810:Therapeutic Equivalency
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D013607:Tablets; D044005:Tetrahydroisoquinolines; C054501:quinaprilat; D000077583:Quinapril