Impaired bioavailability of rifampicin in presence of isoniazid from fixeddose combination (FDC) formulation

The present study describes comparative bioavailability of rifampicin (RIF) after administration of a single component RIF (450 mg) capsule and rifamp icin-isonizid (RIF-INH) (450 + 300 mg) fixed dose combination (FDC) capsule formulations. Six healthy male volunteers participated in a single dose, t wo treatment, two period, cross-over study. A sensitive, specific and accur ate HPTLC method was developed, validated and employed for estimation of RI F and its major active metabolite, 25-Desacetylrifampicin (25-DAR) levels, in urine. Using the urinary excretion data various pharmacokinetic paramete rs: AUC(0-24), AUC(0) cumulative amount excreted in 24 h. peak excretion ra te. etc. for both RIF and 25-DAR were calculated and compared statistically (ANOVA, 90% confidence interval for ratio). Significant decrease in the bi oavailability ( similar to 32% as RIF and similar to 28% as 25-DAR) of RIF from FDC capsules was observed. The present bioavailability study confirms our serious doubts about the stability of RIF in presence of INH in acidic environment of stomach, which probably is the main factor responsible for t he reduced bioavailability of RIF from RIF-INH combination formulations. Th is study underlines the fact that there is an urgent need to reconsider the formulation of the FDC product in order to minimize or avoid the decomposi tion of RIF in gastrointestinal tract. (C) 2001 Elsevier Science B.V. All r ights reserved.