Interaction of rifampicin with other drugs.
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Biomedical subjects
Publications and source records attributed to G Acocella.
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The incidence of primary resistance to rifampicin in Mycobacterium tuberculosis has been analysed in countries where rifampicin is restricted to use for treating tuberculosis and in countries where its use is not restricted. There is no evidence that rifampicin-resistant M tuberculosis strains are more common where the use of the drug is unrestricted. Resistance to rifampicin is less common than is resistance to streptomycin or to isoniazid. We can thus see no danger of producing resistant strains of M tuberculosis if rifampicin therapy is used for short periods for non-tuberculosis infections. The problem of resistance mutants arising in the non-tuberculous species being treated is overcome by combining rifampicin with trimethoprim.
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Data on the incidence of primary resistance to rifampicin in Mycobacterium tuberculosis strains have been collected from various countries. Strains isolated from those countries where rifampicin is used for both tuberculous and non-tuberculous conditions (Italy, Argentina, Brazil, and Spain) did not show a higher incidence of primary resistance than did strains from other countries (France, U.K., and U.S.A.) where rifampicin use is confined to tuberculosis. It is concluded that there is no evidence to justify fears of an increased incidence of resistance to rifampicin in M. tuberculosis if rifampicin were used discreetly for treating non-tuberculous infections.
Two studies were carried out in man with the aim of assessing the serum and urine concentrations of rifampicin administered by i.v. infusion. In patients suffering from various diseases, a dose of 600 mg i.v. proved to be equieffective with a 600 mg oral dose. Repeated administration of a 600 mg dose by i.v. infusion for a week produced serum levels corresponding to those achieved by oral administration. With the i.v. preparation the drop in serum rifampicin levels during continuous administration was less marked than with the oral administration. The recovery of antibiotic in the urine seems to be lower with i.v. than with the oral preparation. The i.v. preparation was very well tolerated by all the patients.
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The possible existence of kinetic interactions between rifampicin and isoniazid and the effect of the concomitant presence of an impaired liver function were investigated in man. In a first study normal healthy subjects and patients with chronic liver disease received, on three different occasions, a single dose of 600 mg rifampicin or isoniazid and of rifampicin and isoniazid associated in randomized sequences. The results have shown that in both groups the serum levels, half-life values, and urinary excretion of each drug given alone are not significantly different from those observed when the other drug is associated. Serum levels and half-life of rifampicin and isoniazid were significantly higher in patients with chronically impaired liver. In a second study, rifampicin and isoniazid were given in combination at the same doses as in the first study over a period of one week. The results have shown a trend to decrease in the serum levels of rifampicin of the healthy subjects and a trend to increase in the patients with chronic liver disease on day 7 of treatment. In both groups a reduction in the half-life of rifampicin was also observed. No changes in serum isoniazid concentrations were observed between day 1 and day 7 in the healthy subjects, whereas a significant increase was observed in the patients. No significant changes in the half-life of isoniazid were observed.
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