Single-dose randomized, open-label, 2-way crossover bioequivalence study of clopidogrel 75 mg tablet in healthy volunteers under fasting conditions.
OBJECTIVE
This study aimed to assess the bioequivalence of 2 formulations of 75 mg clopidogrel hydrogen sulphate film-coated tablet, under fasting conditions.


METHODS
64 healthy subjects, age ranging from 19 to 55 years, were enrolled in a single-centre, randomized, single-dose, open-label, 2-way crossover study, with a minimum washout period of 7 days. Plasma samples were collected up to 24 h post dosing. Clopidogrel and clopidogrel carboxylic acid levels were determined by reverse-phase high-performance chromatography coupled to tandem mass spectrometry detection, LC-MS-MS method. Pharmacokinetic parameters used for bioequivalence assessment were the AUClast (area under the concentration-time curve from time zero to time of last observed nonzero concentration) and the Cmax (maximum observed concentration). These parameters were determined from the clopidogrel concentration data using non-compartmental analysis as well for clopidogrel carboxylic acid concentration data.


RESULTS
The 90% CI (90% confidence intervals), obtained by analysis of variance (ANOVA) were within the predefined ranges (80.00 - 125.00%) for both analytes.


CONCLUSIONS
Bioequivalence between test and formulations, under fasting conditions, was concluded both in terms of rate and extent of absorption.
Filipe
A
A
Medical Department, Grupo Tecnimede, Abrunheira, Sintra, Portugal. dmed.ct@tecnimede.pt
Almeida
S
S
Franco Spínola
A C
AC
Neves
R
R
Tanguay
M
M
Jiménez
C
C
Shink
E
E
D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D000077144:Clopidogrel; D018592:Cross-Over Studies; D005215:Fasting; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D010975:Platelet Aggregation Inhibitors; D013607:Tablets; D000077144:Clopidogrel; D013988:Ticlopidine