1 The urinary metabolite profile of isoniazid has been studied in patients receiving the drug as therapy for tuberculosis and the profile in patients suffering liver damage due to isoniazid compared with that in control patients.
2 There were no consistent differences between control patients and those suffering liver damage in the excretion of isoniazid metabolites.
3 It may be that susceptibility to the hepatotoxicity of isoniazid is not due to metabolic differences, although a number of other possible explanations are discussed.
4 It is not at present possible to predict which patients will be susceptible from metabolic studies.
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.
Gronhagen-Riska, C., Hellstrom, P.E. & Froseth, B. (1978). Predisposing factors in hepatitis induced by isoniazid-rifampicin treatment of tuberculosis. Am. Rev. Respir. Dis., 118, 461-466.
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.
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.
10.
Musch, E., Eichelbaum, M., Wang, J.K., Sassen, W.V., Castro-Parra, M. & Dengler, H.J. (1982). Incidence of hepatotoxic side effects during antituberculous therapy (INH, RMP, EMB) in relation to the acetylator phenotype. Klin. Wochenschr., 60, 513-519.
11.
Nelson, S.D., Mitchell, J.R., Timbrell, J.A., Snodgrass, W.R. & Corcoran, G.B. (1976). Isoniazid and iproniazid: activation of metabolites to toxic intermediates in man and rat. Science, 193, 901-903.
12.
Ohnaus, E.E. & Park, B.K. (1979). Measurement of urinary 6β-hydroxycortisol excretion as an in vivo parameter of the clinical assessment of the microsomal enzyme inducing capacity of antipyrine, phenobarbitone and rifampicin. Eur. J. Clin. Pharmacol., 13, 139-145.
13.
Siersback-Nielsen, K., Molholm Hansen, J., Kampinann, J. & Kristensen, M. (1971). Rapid evaluation of creatinine clearance. Lancet, i, 1133-1134.
14.
Timbrell, J.A., Wright, J.M. & Baillie, T.A. (1977a). Monoacetylhydrazine as a metabolite of isoniazid in man. Clin. Pharmacol. Ther., 22, 602-608.
15.
Timbrell, J.A., Wright, J.M. & Smith, C.M. (1977b). Determination of hydrazine metabolites of isoniazid in human urine by gas chromatography. J. Chromatogr., 138, 165-172.
16.
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.
