Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers.
OBJECTIVE
To assess the bioavailability of rifampicin (RMP) in three brands of combination formulations of anti-tuberculosis drugs.


METHODS
A three-way double-blind, cross-over bioavailability study of RMP and isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods.


RESULTS
The mean values of RMP in brand N (Cmax 6.49+/-0.52 microg/mL, Tmax 2.33+/-0.18 h, AUC(0-24h) 39.83+/-3.44 microg/mL.h) were comparable with those obtained with brand R (Cmax 5.22+/-0.59 microg/mL, Tmax 2.50+/-0.12 h, AUC(0-24h) 33.33+/-3.47 microg/mL.h). The mean values of RMP in brand L (Cmax 3.05+/-0.52 microg/ mL, Tmax 3.79+/-0.57 h and AUC(0-24h) 21.78+/-3.67 microg/ mL.h) were significantly different from those in brand R. Nevertheless, all of the pharmacokinetic parameters obtained for INH and ACINH in all three brands were comparable.


CONCLUSIONS
Using brand R as a comparison, brand N was bioequivalent and brand L was not bioequivalent.
Padgaonkar
K A
KA
Department of Clinical Pharmacology, LTM Medical College, Sion Hospital, Mumbai, India.
Revankar
S N
SN
Bhatt
A D
AD
Vaz
J A
JA
Desai
N D
ND
D'Sa
S
S
Shah
V
V
Gandewar
K
K
D000293:Adolescent; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D012016:Reference Values; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004338:Drug Combinations; D007538:Isoniazid; D012293:Rifampin