Stereospecific versus nonstereospecific assessments for the bioequivalence of two formulations of racemic chlorpheniramine.
Chlorpheniramine (chlorphenamine, CPAM) is a racemic antihistaminic H1 drug containing two enantiomers. The aim of this study was to assess the bioequivalence of two formulations (reference and Vietnamese-tested formulation) of racemic chlorpheniramine combined with phenylpropanolamine in an open-labeled, randomized, crossover two-period study, after administration of 8 mg of racemic chlorpheniramine in 12 healthy Vietnamese subjects. First, dissolution of both formulations was tested in vitro according to USP requirements. Then the 12 subjects received both formulations after an overnight fast and a 7-day wash-out period. Plasma samples were collected up to 168 h. Plasma concentrations of total chlorpheniramine and its individual enantiomers were determined with a validated chiral HPLC method and pharmacokinetic parameters were estimated using model-independent analysis. For the reference formulation, Cmax and AUC values were higher for (+)S-chlorpheniramine ((+)S-CPAM) compared to (-)R-chlorpheniramine ((-)R-CPAM) (13.3 vs. 6.8 ng/ml and 409 vs. 222 ng/ml/h, respectively) while Clt/F and Vd/F were lower (9.8 vs. 17.6 l/h and 321 vs. 627 l, respectively). No difference was observed for Tmax, t(1/2), and MRT. Pharmacokinetic parameters were similar for the reference and the Vietnamese-tested formulation. Bioequivalence was assessed by Schuirmann test, as recommended by the current FDA and European Community criteria. Dissolution tests showed that both formulations were equivalent. A nonstereospecific, but not a stereospecific, approach indicated bioequivalence between the formulations.
Bui
T H
TH
Pitié Salpêtrière Hospital, Pharmacy, Paris, France.
Fernandez
C
C
Vu
K
K
Nguyen
K H
KH
Thuillier
A
A
Farinotti
R
R
Arnaud
P
P
Gimenez
F
F
D000328:Adult; D002744:Chlorpheniramine / Q000737:chemistry / Q000493:pharmacokinetics* / Q000592:standards; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004339:Drug Compounding; D006634:Histamine H1 Antagonists / Q000737:chemistry / Q000493:pharmacokinetics* / Q000592:standards; D006801:Humans; D008297:Male; D012015:Reference Standards; D013237:Stereoisomerism; D013810:Therapeutic Equivalency
D006634:Histamine H1 Antagonists; D002744:Chlorpheniramine