Bioavailability of rifampicin in a separate formulation and fixed dose combination with isoniazid NIH: a case for a fixed dose combination (FDC) for the treatment of tuberculosis.
OBJECTIVE
To study and compare the bioavailability of rifampicin (RIF), in two locally manufactured formulations; an FDC and a separate formulation and an imported FDC formulation.


METHODS
Open within subjects, single blind cross over study.


METHODS
Each volunteer subject, acting as their own control, received the two fixed dose combinations and the separate formulation with the same amount of 450 mg RIF.


METHODS
Cmax (peak drug concentration achieved), Tmax (time at which peak drug concentration is achieved), T1/2el (biological half-life of elimination) and area under the curve (AUC) for zero to 10 hours and zero to infinity. These are obtained from plotting plasma concentration against time.


RESULTS
There was a significant difference in the Cmax between free and RIF combined with INH (6.1 and 7.6 mg/l respectively) and no significant difference in the other parameters measured, of the local products. Comparison of the local products and imported product showed no significant difference in AUC but significant differences in T1/2el, C max and Tmax (p = 0.003, 0.041 and 0.025 respectively).


CONCLUSIONS
The Zimbabwe manufactured and the German products had "demonstrable bioavailability" as defined by the International Union Against Tuberculosis and Lung Diseases (IUATLD). The local manufacturer appeared to have the technological capability to produce a registrable combined RIF/INH table to be used in the treatment of tuberculosis and to prevent the irrational use of RIF.
Nyazema
N Z
NZ
Department of Clinical Pharmacology, University of Zimbabwe Medical School, Avondale, Harare.
Rabvukwa
P
P
Gumbo
J
J
Ndudzo
P
P
Chitemerere
C
C
D000328:Adult; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000600:supply & distribution; D000995:Antitubercular Agents / Q000008:administration & dosage*; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage*; D008297:Male; D008657:Metabolic Clearance Rate; D012293:Rifampin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000600:supply & distribution; D016037:Single-Blind Method; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy*
D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin