Bioavailability of rifampicin capsules

Abstract

In a 3-year bioavailability program 14 studies in 45 healthy volunteers were carried out to differentiate between experimental lots of rifampicin (RMP) capsules and marketed preparations of other manufacturers with lower bioavailability than Rifadin (RFD), used as standard reference drug. In each study single oral doses of 600 mg of 2-5 different RMP preparations were administered to 6-12 volunteers in fasting conditions according to a balanced crossover design. The pharmacokinetic parameters of RFD capsules were practically identical for the same batch tested at different times and for several batches tested in different groups of subjects. Variations in particle size, excipients, or manufacturing process of the experimental preparations or capsules marketed by other manufacturers produced a marked change in bioavailability of RMP. An additional study in four volunteers given 450 mg RMP confirmed that the absorption of RMP is less when the drug is taken with food. It is concluded that due to the wide variability in individual serum levels reported in the literature, some patients who absorb RMP poorly may be given ineffective therapy, especially when there are several concomitant unfavorable factors, such as a poor drug product or the effect of food.