Background & Objectives: Poor bioavailability of rifampicin (R) in combination with other
anti-tuberculosis drugs such as isoniazid (H), pyrazinamide (Z), and ethambutol (E) is a subject of
much concern for the last few decades. This could be due to an interaction between R and other drugs.
An investigation was therefore undertaken to examine the bioavailability of R in the presence of H, Z
and E or a combination of the three drugs.
Methods: The study included eight healthy volunteers, each being investigated on four occasions at
weekly intervals once with R alone and with three of the four combinations on the three remaining
occasions. A partially balanced incomplete block design was employed and the allocation of R or the
drug combinations was random. Plasma concentrations of R at intervals upto 12 h were determined by
microbiological assay using Staphylococcus aureus as the test organism. The proportion (%) dose of R
as R plus desacetyl R (DR) in urine excreted over the periods 0-8 and 8-12 h was also determined.
Bioavailability was expressed as an index (BI) of area under time concentration curve (AUC) calculated
from the plasma concentrations or proportion of dose of R excreted as R plus DR in urine with the
combinations to that with R alone.
Results: The bioavailability indices based on AUC were 0.96 with RE, 0.76 with RH, 1.08 with RZ and
0.65 with REHZ. The indices based on urine estimations (0-8 h) were similar, the values being 0.94,
0.84, 0.94 and 0.75, respectively. A second investigation revealed that the decrease of bioavailability of
R with H was not due to the excipients present in H tablets.
Interpretation & conclusion: Isoniazid alone or in combination with E and Z reduces the bioavailability
of R. Urinary excretion data offer a simple and non invasive method for the assessment of bioavailability
of R