Comparative bioavailability study with two chlorpropamide tablet formulations in healthy volunteers.
OBJECTIVE
The aim of this study was the assessment of the bioequivalence of two formulations (250 mg tablet) of chlorpropamide (CAS 94-20-2) in 36 healthy volunteers of both sexes.


METHODS
The study was conducted using an open, randomized, two-period crossover design with a 3-week washout interval. Plasma samples were obtained over a 72-h period. Plasma chlorpropamide concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reaction monitoring (MRM). From the chlorpropamide plasma concentration vs time curves, the following pharmacokinetic parameters were obtained: AUC(0-72h), AUC(inf) and C(max).


RESULTS
The limit of quantification was 0.1 microg/mL for plasma chlorpropamide analysis. The geometric mean and respective 90 % confidence interval (CI) of Test/ Reference percent ratios were 93.99% (87.11%-101.41%) for C(max), 92.45% (85.96%-99.44%) for AUC(0-72h) and 90.30% (83.35%-97.82%) for AUC(0-inf).


CONCLUSIONS
Since the 90 % CI for AUC(0-72h), AUC(0-inf) and C(max) ratios were within the 80-125%interval proposed by the US FDA, it was concluded that chlorpropamide 250 mg tablet (test formulation) was bioequivalent to the reference 250 mg tablet for of both the rate and extent of absorption.
da Silva
Marcia Aparecida
MA
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
Mendes
Fabiana D
FD
de Oliveira
Rogério Antonio
RA
Monif
Tausif
T
Patni
Anil
A
Reyar
Simrit
S
Mendes
Gustavo D
GD
De Nucci
Gilberto
G
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002747:Chlorpropamide / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization; D013607:Tablets; D053719:Tandem Mass Spectrometry
D007004:Hypoglycemic Agents; D013607:Tablets; D002747:Chlorpropamide