1 The effect of rifampicin on the metabolism of isoniazid in human volunteer subjects has been investigated.
2 The urinary metabolites of isoniazid after a single dose and after six daily doses of isoniazid plus rifampicin were examined.
3 The isoniazid-rifampicin combination clearly increased the ratio of urinary 6-β-hydroxycortisol to 17-hydroxycorticosteroids, indicating that induction of the microsomal enzymes had occurred.
4 However, no significant changes in the urinary metabolites of isoniazid were detected, and therefore it is not possible to predict the effect of rifampicin on isoniazid hepatotoxicity.
Dymond, L.C. & Russell, D.W. (1970). Rapid determination of isonicotinic acid hydrazide in whole blood with 2,4,6-trinitrobenzenesulphonic acid. Clin. Chim. Acta, 27, 513-520.
3.
Eidus, L., Harnanansingh, A.M.T. & Jessamine, A.G. (1971). Urine test for phenotyping isoniazid inactivators. Am. Rev. Respir. Dis., 104, 587-591.
4.
Ellard, G.A. & Gammon, P.T. (1976). Pharmacokinetics of isoniazid metabolism in man . J. Pharmacokinet. Biopharm., 4, 83-113.
5.
Girling, D.J. (1978). The hepatic toxicity of antituberculous regimens containing isoniazid, rifampicin and pyrazinamide. Tubercle , 59, 13-32.
6.
Heubel, F. & Netter, K.J. (1979). Atypical inductive properties of rifampicin. Biochem. Pharmacol., 28, 3373-3378.
7.
Horai, Y., Ishizaki, T., Sasaki, T., Koga, G., Matsuyama, K. & Iguchi, S. (1982). Isoniazid disposition, comparison of isoniazid phenotyping methods in and acetylator distribution of Japanese patients with idiopathic systemic lupus erythematosus and control subjects. Br. J. Clin. Pharmacol., 13, 361-374.
8.
Lees, A.W., Allan, G.W., Smith, J., Tyrrel, W.F. & Fallon, R.J. (1971). Toxicity of rifampicin plus isoniazid and rifampicin plus ethambutol therapy. Tubercle, 52, 182-190.
Mitchell, J.R., Thorgiersson, U.P., Black, M., Timbrell, J.A., Snodgrass, W.R., Potter, W.Z., Jollow, D.J. & Keiser, H. (1975). Increased incidence of isoniazid hepatitis in rapid acetylators: possible relation to hydrazine metabolites. Clin. Pharmacol. Ther., 18, 70-79.
11.
Ohnhaus, E.E. & Park, B.K. (1979). Measurement of urinary 6β-hydroxycortisol excretion as an in vivo parameter in the clinical assessment of the microsomal enzyme inducing capacity of antipyrine, phenobarbitone and rifampicin. Eur. J. Clin. Pharmacol., 13, 139-145.
12.
Park, B.K. (1978). A direct radioimmunoassay for 6β-hydroxycortisol in human urine. J. SteroidBiochem., 9, 963-966.
13.
Perry, W., Jenkins, M.V., Setchell, K.D.R. & Stamp, T.C.B. (1978). Induction and inhibition of hepatic microsomal enzymes by rifampicin and isoniazid. Clin. Sci. Mol. Med. (Abstract), 55, 21-22.
14.
Price-Evans, D.A. (1969). An improved and simplified method of detecting the acetylator phenotype. Med. Genet., 6, 405-407.
15.
Sanghui, A., Wright, C., Parikh, B. & Desai, H. (1973). Urinary 17-hydroxycorticosteroid determination with p-hydrazinobenzenesulphonic acid-phosphoric acid. Am. J. Clin. Pathol., 60, 684-690.
16.
Timbrell, J.A., Wright, J.M. & Baillie, T.A. (1977). Monoacetylhydrazine as a metabolite of isoniazid in man. Clin. Pharmacol. Ther., 22, 602-608.
17.
Timbrell, J.A., Wright, J.M. & Smith, C.M. (1977). Determination of hydrazine metabolites of isoniazid in human urine by gas chromatography. J. Chromatogr., 138, 165-172.
18.
Timbrell, J.A., Mitchell, J.R., Snodgrass, W.R. & Nelson, S.D. (1980). Isoniazid hepatotoxicity: the relationship between covalent binding and metabolism in vivo. J. Pharmacol. Exp. Ther., 213, 364-369.
19.
Tredger, J.M., Smith, H.M., Powell-Jackson, P.R., Davis, M. & Williams, R. (1981). Effect of rifampicin on the mouse hepatic mixed-function oxidase system. Biochem. Pharmacol., 30, 1043-1051.
