Skip to main content

Clinical Pharmacokinetics of Isoniazid

Summary

The pharmacokinetics of isoniazid in man are described. Pronounced interindividual variation in circulating isoniazid concentration and clearance which occur after dosing with the drug are associated with hereditary differences in the acetylalor status. The variations in rate of isoniazid inactivation and elimination in different (rapid and slow) acetylator phenotypes are primarily due to differences in the rate of acetylation of isoniazid by a genetically controlled polymorphic N-acetyltransferase in liver and small intestine. An appreciable ‘first-pass’ effect is observed following oral isoniazid administration, particularly in the rapid acetylator phenotype.

Liver disease can cause a significant prolongation in the clearance of isoniazid; in the acutely ill patient, the prolongation correlates most closely with serum bilirubin elevation, although the degree of prolongation is less important than the intrinsic genetic difference between acetylator phenotypes. The effect of renal impairment on isoniazid excretion is relatively unimportant, even in slow acetylators.

Methods for monitoring blood and urine concentrations of isoniazid and for acetylator phenotype determination which are convenient for the patient and clinician are available. Implications of phenotypic differences in acetylator status for the optimal management of tuberculosis with isoniazid are considered. Attempts to devise new isoniazid formulations for this purpose are being evaluated.

This is a preview of subscription content, access via your institution.

References

  • Airaksinen, E.; Mattila, M.J. and Ollila, O.: Inactivation of isoniazid and sulphadimidine in Mongoloid subjects. Annales Medicinae Internae Fenniae 47: 303–307 (1969).

    CAS  Google Scholar 

  • Albert, A.: The affinity of isonicotinic hydrazide for metals. Experientia 9: 370 (1953).

    PubMed  Article  Google Scholar 

  • Allen, B.W.; Ellard, G.A.; Gammon, P.T.; King, R.C.; McDougall, A.C. and Weddell, A.G.M.: Penetration of dapsone, rifampicin, isoniazid, and pyrazinamide into peripheral nerves. British Journal of Pharmacology 55: 151–155 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Armstrong, A.R. and Pert, H.E.: A comparison between the behavior of Eskimos and non-Eskimos to the administration of isoniazid. American Review of Respiratory Diseases 81: 588–594 (1960).

    CAS  Google Scholar 

  • Bach, P.H.; Higgins-Opitz, S.B.; Bima, B. and Leary, W.P.: Isoniazid acetylation status of black South African tuberculosis patients. South African Medical Journal 50: 1132–1134 (1976).

    PubMed  CAS  Google Scholar 

  • Barclay, W.R.; Ebert, R.H.; LeRoy, G.V.; Manthei, R.W. and Roth, L.J.: Distribution and excretion of radioactive isoniazid in tuberculosis patients. Journal of the American Medical Association 151: 1384–1388 (1953).

    PubMed  CAS  Google Scholar 

  • Barley, J.F.; Evered, D.F. and Tromon, S.M.: Transport of isoniazid across small intestine in vitro. Biochemical Pharmacology 21: 2660–2661 (1972).

    PubMed  CAS  Article  Google Scholar 

  • Bell, J.C.; Riemenschnider, D.K. and Mitchell, N.S.: Effect of certain aromatic amines on serum isoniazid concentrations in tuberculosis patients. American Review of Tuberculosis 76: 152–158 (1957).

    PubMed  CAS  Google Scholar 

  • Boman, G.: Decreased serum concentrations of rifampicin when given with PAS orally; in Morselli, Garratini and Cohen (Eds) Drug Interactions, pp.33–39 (Raven Press, New York 1974).

    Google Scholar 

  • Bowersox, D.W.; Winterbauer, R.H.; Stewart, C.L.; Orme, B. and Barron, E.: Isoniazid dosage in patients with renal failure. New England Journal of Medicine 289: 84–87 (1973).

    PubMed  CAS  Article  Google Scholar 

  • Boxenbaum, H.E. and Riegelman, S.: Pharmacokinetics of isoniazid and some metabolites in man. Journal of Pharmacokinetics and Biopharmaceutics 4: 289–325 (1976).

    Google Scholar 

  • Boxenbaum, H.G.; Bekersky, I.; Mattaliano, V. and Kaplan, S.A.: Plasma and salivary concentrations of isoniazid in man: Preliminary findings in two slow acetylator subjects. Journal of Pharmacokinetics and Biopharmaceutics 3: 443–456 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Brennan, R.W.; Dehejia, H.; Kutt, H.; Verebely, K. and McDowell, F.: Diphenylhydantoin intoxication attendant to slow inactivation of isoniazid. Neurology 20: 687–693 (1970).

    PubMed  CAS  Article  Google Scholar 

  • Buchanan, H.; Strickwold, B. and Shvenyane, E.: Isoniazid inactivation in black patients with tuberculosis. South African Medical Journal 50: 463–465 (1976).

    PubMed  CAS  Google Scholar 

  • Chavan, S.R.; Nikam, ST.; Pradhan, D.V.; Bhide, M.B. and Gaitonde, B.B.: Bio-availability of INH in liquid dosage form. Indian Journal of Physiology and Pharmacology 18: 120–122 (1974).

    PubMed  CAS  Google Scholar 

  • Danysz, A. and Wisniewski, K.: Control of drug transport through cell membranes. Materia Medica Polona 2: 35–44 (1970).

    Google Scholar 

  • Des Prez, R. and Boone, I.V.: Metabolism of 14C-isoniazid in humans. American Review of Respiratory Diseases 84: 42–51 (1961).

    Google Scholar 

  • Devadatta, S.; Gangadharam, P.R.J.; Andrews, R.H.; Fox, W.; Ramakrishnan, C.V.; Selkon, J.B. and Vela, S.: Peripheral neuritis due to isoniazid. Bulletin of the World Health Organization 23: 587–598 (1960).

    PubMed  CAS  Google Scholar 

  • Dufour, A.P.; Knight, R.A. and Harris, H.W.: Genetics of isoniazid metabolism in Caucasian, Negro, and Japanese populations. Science 145: 391 (1964).

    PubMed  CAS  Article  Google Scholar 

  • Eidus, L. and Hodgkin, M.M.: A new isoniazid preparation designed for moderately fast and ‘fast’ metabolizers of the drug. Arzneimittel-Forschung 25: 1077–1080 (1975).

    PubMed  CAS  Google Scholar 

  • Eidus, L.; Ling, G.M. and Harnanansingh, A.M.T.: Isoniazid excretion in fast and slow inactivators and its practical aspect for phenotyping. Arzneimittel-Forschung 21: 1696–1699 (1971).

    CAS  Google Scholar 

  • Eidus, L.; Varughese, P.; Hodgkin, M.M.; Hsu, A.H.E. and MacRae, K.B.: Simplification of isoniazid phenotyping procedure to promote its application in the chemotherapy of tuberculosis. Bulletin of the World Health Organization 49: 507–516 (1973).

    PubMed  CAS  Google Scholar 

  • Eidus, L.; Hodgkin, M.M.; Hsu, A.H.E. and Schaefer, O.: Pharmacokinetic studies with an isoniazid slow-releasing matrix preparation. American Review of Respiratory Diseases 110: 34–42 (1974a).

    CAS  Google Scholar 

  • Eidus, Jl.; Hodgkin, M.M.; Schaefer, O. and Jessamine, A.G.: Distribution of isoniazid inactivators determined by Eskimos and Canadian college students by a urine test. Review of Canadian Biology 33: 117–123 (1974b).

    CAS  Google Scholar 

  • Eidus, L.; Ling, G.M. and Hodgkin, M.M.: Effect of isoniazid matrix preparation on human blood levels. Proceedings of the 8th International CKONGRESS OF Chemotherapy 1: 696–707 (1974c).

    CAS  Google Scholar 

  • Eidus, L.; Glatthaar, E.; Hodgkin, M.M.; Nel, E.E. and Kleeberg, H.H.: Phenotyping of South African black tuberculosis patients for inactivation of isoniazid. Research Communications in Chemical Pathology and Pharmacology. In press (1979).

  • Ellard, G.A.: Variations between individuals and populations in the acetylation of isoniazid and its significance for treatment of pulmonary tuberculosis. Clinical Pharmacology and Therapeutics 19: 610–625 (1976a).

    PubMed  CAS  Google Scholar 

  • Ellard, G.A.: A slow release preparation of isoniazid: pharmacological aspects. Bulletin of the International Union Against Tuberculosis 51: 143–154 (1976b).

    Google Scholar 

  • Ellard, G.A. and Gammon, P.T.: Pharmacokinetics of isoniazid metabolism in man. Journal of Pharmacokinetics and Biopharmaceutics 4: 83–113 (1976).

    PubMed  CAS  Article  Google Scholar 

  • Ellard, G.A. and Gammon, P.T.: Acetylator phenotyping of tuberculosis patients using matrix isoniazid or sulphadimidine and its prognostic significance for treatment with several intermittent isoniazid-containing regimens. British Journal of Clinical Pharmacology 4: 5–14 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Ellard, G.A.; Gammon, P.T.; Lakshminarayan, S.; Fox, W.; Aber, V.R.; Mitchison, D.A.; Citron, K.M. and Tall, R.: Pharmacology of some slow-release preparations of isoniazid of potential use in intermittent treatment of tuberculosis. Lancet 1: 340–343 (1972a).

    PubMed  CAS  Article  Google Scholar 

  • Ellard, G.A.; Gammon, P.T. and Wallace, S.M.: The determination of isoniazid and its metabolites acetylisoniazid, monoacetyl hydrazine, diacetylhydrazine, isonicotinic acid, and isonicotinyl-glycine in serum and urine. Biochemical Journal 26: 449–458 (1972b).

    Google Scholar 

  • Ellard, G.A.; Gammon, P.T.; Polansky, F.; Viznerova, A.; Havlik, I. and Fox, W.: Further studies on the pharmacology of slow-release matrix preparations of isoniazid (Smith and Nephew No 582) of potential use in the intermittent treatment of tuberculosis. Tubercle 54: 57–66 (1973a).

    PubMed  CAS  Article  Google Scholar 

  • Ellard, G.A.; Gammon, P.T. and Tiitinen, H.: Determination of the acetylator phenotype from the ratio of the urinary excretion of acetylisoniazid to acid-labile isoniazid: A study in Finnish Upland. Tubercle 54: 201–210 (1973b).

    PubMed  CAS  Article  Google Scholar 

  • Ellard, G.A.; Gammon, P.T. and Tiitinen, H.: Determination of the acetylator phenotype using matrix isoniazid. Tubercle 56: 203–209 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Euard, G.A.; Mitchison, D.A.; Girling, D.J.; Nunn, A.J. and Fox, W.: The hepatic toxicity of isoniazid among rapid and slow acetylators of the drug. American Review of Respiratory Diseases 118: 628–629 (1978).

    Google Scholar 

  • Elmendorf, D.F.; Cawthon, W.V.; Muschenheim, C. and McDermott, W.: The absorption, distribution, excretion, and shortterm toxicity of isonicotinic acid hydrazide (Nydrazid) in man. American Review of Tuberculosis 65: 429–442 (1952).

    PubMed  CAS  Google Scholar 

  • Evans, D.A.P.: Pharmacogenetique. Medecine et Hygiene 20: 905–921 (1962).

    Google Scholar 

  • Evans, D.A.P.: Individual variations of drug metabolism as a factor in drug toxicity. Annals of the New York Academy of Sciences 123: 178–181 (1965).

    PubMed  CAS  Article  Google Scholar 

  • Evans, D.A.P.: An improved and simplified method of detecting the acetylator phenotype. Journal of Medical Genetics 6: 405–407 (1969).

    PubMed  CAS  Article  Google Scholar 

  • Evans, D.A.P. and White, T.A.: Human acetylation polymorphism. Journal of Laboratory and Clinical Medicine 63: 430–435 (1964).

    Google Scholar 

  • Evans, D.A.P.; Manley, K.A. and McKusik, V.A.: Genetic control of isoniazid metabolism in man. British Medical Journal 2: 485–491 (1960).

    PubMed  CAS  Article  Google Scholar 

  • Eze, L.C. and Evans, D.A.P.: The use of the autoanalyzer to determine the acetylator phenotype. Journal of Medical Genetics 7: 57–59 (1972).

    Article  Google Scholar 

  • Farah, F.; Taylor, W.; Rawlins, M.D. and James, O.: Hepatic drug acetylation and oxidation: Effects of aging in man. British Medical Journal 2: 155–156 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Fawcett, I.W. and Gammon, P.T.: The determination of the acetylator phenotype in a northern Nigerian population. Tubercle 56: 199–201 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Fine, A. and Sumner, D.J.: Determination of acetylator status in uremia. British Journal of Clinical Pharmacology 2: 475–476 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Gangadharam, P.R.J. and Selkon, J.B.: The association between response to treatment with isoniazid and the rate of inactivation of isoniazid in South Indian patients with pulmonary tuberculosis. Bulletin of the International Union Against Tuberculosis 32: 556–559 (1962).

    Google Scholar 

  • Gardiner, T.H. and McAnalley, B.H.: Effect of lung edema on the pulmonary absorption of drugs. Life Sciences 23: 1827–1833 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Geering, J.M.; Ruch, W. and Dettli, L.: Diphenylhydantoin poisoning due to diphenylhydantoin-isoniazid interaction. Schweizerische Medizinische Wochenschrift 104: 1224–1228 (1974).

    PubMed  CAS  Google Scholar 

  • Gelber, R.; Jacobsen, P. and Levy, L.: A study of the availability of six commercial formulations of isoniazid. Clinical Pharmacology and Therapeutics 10: 841–848 (1969).

    PubMed  CAS  Google Scholar 

  • Glowinski, I.B.; Radtke, H.E. and Weber, W.W.: Genetic variation in N-acetylation of carcinogenic arylamines by human and rabbit liver. Molecular Pharmacology 14: 940–949 (1978).

    PubMed  CAS  Google Scholar 

  • Gold, C.H.; Buchanan, N.; Tringham, V.; Viljoen, M.; Struckwold, B. and Moodley, G.P.: Isoniazid pharmacokinetics in patients in chronic renal failure. Clinical Nephrology 6: 365–369 (1976).

    PubMed  CAS  Google Scholar 

  • Gronhagen-Riska, C.; Hellstrom, P.E. and Froseth, B.: Predisposing factors in hepatitis induced by isoniazid-rifampin treatment of tuberculosis. American Review of Respiratory Diseases 18: 461–466 (1978).

    Google Scholar 

  • Hanngren, A.; Borga, O. and Sjoqvist, F.: Inactivation of isoniazid (INH) in Swedish tuberculosis patients before and during treatment with para-aminosalicylic acid (PAS). Scandinavian Journal of Respiratory Diseases 51: 61–69 (1970).

    PubMed  CAS  Google Scholar 

  • Harris, H.W.: Isoniazid metabolism in humans: Genetic control, variation among races and influence of chemotherapy of tuberculosis. Bulletin of the International Union Against Tuberculosis 32: 503–507 (1962).

    Google Scholar 

  • Hashem, N.; Khalifa, S. and Nour, A.: The frequency of isoniazid acetylase enzyme deficiency among Egyptians. American Journal of Physical Anthropology 31: 97–102 (1969).

    PubMed  CAS  Article  Google Scholar 

  • Hayward, G.A.: Human acetylation polymorphism in Polynesians. Proceedings of the University of Otago Medical School 53: 67–68 (1975).

    Google Scholar 

  • Hearse, D.J. and Weber, W.W.: Multiple N-acetyltransferases and drug metabolism: Tissue distribution, characterization and significance of mammalian N-acetyltransferase. Biochemical Journal 132: 519–526 (1973).

    PubMed  CAS  Google Scholar 

  • Huffman, D.H. and Dujovne, C.A.: The instability of isoniazid and acetylisoniazid in frozen plasma. Research Communications in Chemical Pathology and Pharmacology 15: 203–204 (1976).

    PubMed  CAS  Google Scholar 

  • Hurwitz, A. and Schlozman, D.L.: Effects of antacids on gastrointestinal absorption of isoniazid in rat and man. American Review of Respiratory Diseases 109: 41–47 (1974).

    CAS  Google Scholar 

  • Jeanes, C.W.L.; Schaefer, O. and Eidus, L.: Inactivation of isoniazid by Canadian Eskimos and Indians. Canadian Medical Association Journal 106: 331–335 (1972).

    PubMed  CAS  Google Scholar 

  • Jenne, J.W.: Studies of human patterns of isoniazid metabolism using an intravenous fall-off technique with a chemical method. American Review of Respiratory Diseases 81: 1–8 (1960).

    CAS  Google Scholar 

  • Jenne, J.W.: Partial purification and properties of the isoniazid transacetylase in human liver. Its relationship to the acetylation of p-aminosalicylic acid. Journal of Clinical Investigation 44: 1992–2002 (1965).

    CAS  Article  Google Scholar 

  • Jenne, J.W.; MacDonald, F.M. and Mendoza, E.: A study of the renal clearances, metabolic activation rates, and serum fall-off interaction of isoniazid and para-aminosalicylic acid in man. American Review of Respiratory Diseases 84: 178–371 (1960).

    Google Scholar 

  • Knight, R.A.; Selin, M.J. and Harris, H.W.: Genetic factors influencing isoniazid blood levels in humans. Veterans Administration 18th Conference of Chemotherapy of Tuberculosis, pp.52–58 (ed. by V.A. Department of Medicine and Surgery, Central Office, Washington, D.C. 1959).

    Google Scholar 

  • Kutt, H.; Brennan, R.; Dehejia, H. and Verebely, K.: Diphenylhydantoin intoxication. A complication of isoniazid therapy. American Review of Respiratory Diseases 101: 377–383 (1970).

    CAS  Google Scholar 

  • Lal, S.; Singhal, S.N.; Burley, D.M. and Crossley, G.: Effect of rifampicin and isoniazid on liver function. British Medical Journal 1: 148–150 (1972).

    PubMed  CAS  Article  Google Scholar 

  • Lester, D.: The acetylation of isoniazid in alcoholics. Quarterly Journal of Studies on Alcohol 25: 541–543 (1964).

    PubMed  CAS  Google Scholar 

  • Levi, A.J.; Sherlock, S. and Walker, D.: Phenylbutazone and isoniazid metabolism in patients with liver disease in relation to previous drug therapy. Lancet 1: 1275 (1968).

    PubMed  CAS  Article  Google Scholar 

  • Lloyd, J. and Mitchison, D.A.: A vertical diffusion method for the micro-biological assay of isoniazid. Journal of Clinical Pathology 17: 622–626 (1964).

    PubMed  CAS  Article  Google Scholar 

  • Lunde, P.K.M.; Frislid, K. and Hansteen, V.: Disease and acetylation polymorphism. Clinical Pharmacokinetics 2: 182–197 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Maher, J.R.; Whitney, J.M.; Chambers, J.S. and Stanonis, D.I.: The quantitative determination of isoniazid and paraaminosalicylic acid in body fluids. American Review of Tuberculosis 76: 852–861 (1957).

    PubMed  CAS  Google Scholar 

  • Mattila, M.J. and Tiitinen, H.: The rate of isoniazid inactivation in Finnish diabetic and non-diabetic patients. Annales Medicinae Internae Fenniae 45: 423–427 (1967).

    CAS  Google Scholar 

  • Mattila, M.J. and Takki, S.: Half-lives of isoniazid and salicylic acid in serum and their modification by different drugs in psychiatric patients. Annales Medicinae Intemae Fenniae 47: 124–128 (1969).

    CAS  Google Scholar 

  • Mattila, M.J.; Friman, A.; Larmi, T.K.I. and Koskinen, R.: Absorption of ethionamid, isoniazid, and aminosalicylic acid from the post-resection gastrointestinal tract. Annales Medicinae Internae Fenniae 47: 209–212 (1969).

    CAS  Google Scholar 

  • Melander, A.; Danielson, K. and Hanson, A.: Reduction of isoniazid bioavailability in normal men by concomitant intake of food. Acta Medica Scandinavica 200: 93–97 (1976).

    PubMed  CAS  Article  Google Scholar 

  • Miceli, J.N.; Olson, W.A. and Weber, W.W.: An improved microspectrofluorometric assay for determining isoniazid in serum. Biochemical Medicine 12: 348–355 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Mitchell, J.R.; Thorgeirsson, S.P.; Black, M.; Timbrell, J.A.; Snodgrass, W.R.; Potter, W.Z.; Jollow, D.J. and Kaiser, H.R.: Increased incidence of isoniazid hepatitis in rapid acetylators: Possible relation to hydrazine metabolites. Clinical Pharmacology and Therapeutics 18: 70–79 (1975).

    PubMed  CAS  Google Scholar 

  • Mitchell, J.R.; Zimmerman, H.J.; Ishak, K.G.; Thorgeirsson, S.P.; Timbrell, J.A.; Snodgrass, W.R. and Nelson, S.D.: Isoniazid liver injury: Clinical spectrum, pathology and probable pathogenesis. Annals of Internal Medicine 84: 181–192 (1976).

    PubMed  CAS  Google Scholar 

  • Mitchell, R.S. and Bell, J.C.: Clinical implications of isoniazid blood levels in pulmonary tuberculosis. New England Journal of Medicine 257: 1066–1070 (1957).

    PubMed  CAS  Article  Google Scholar 

  • Mitchell, R.S.; Bell, J.C. and Riemensheider, D.K.: Further observations with isoniazid inactivation tests. Veterans Administration Conference of Chemotherapy of Tuberculosis 19: 62–66 (ed. by Department of Medicine and Surgery, Central Office, Washington, D.C. 1968).

    Google Scholar 

  • Modai, J.; Coulaud, J.P.; Vivien, J.M.; Berthelot, G. and Bergogne-Berezen, E.: The influence of rifampicin upon the metabolism of isoniazid. Nouvelle Presse Medicale 7: 1263–1267 (1978).

    PubMed  CAS  Google Scholar 

  • Noda, A.; Goromaru, T.; Matsuyama, K.; Sogabe, K.; Hsu, K. and Iguchi, S.: Quantitative determination of hydrazides derived from isoniazid in patients. I. Journal of Pharmacobiodynamics 1: 132–141 (1978).

    CAS  Article  Google Scholar 

  • Ogg, C.S.; Toseland, P.A. and Cameron, J.S.: Pulmonary tuberculosis in a patient on intermittent hemodialysis. British Medical Journal 2: 283–284 (1968).

    PubMed  CAS  Article  Google Scholar 

  • Olsen, H. and Mørland, J.: Ethanol-induced increase in drug acetylation in man and isolated rat liver. British Medical Journal 2: 1260–1262 (1978).

    PubMed  CAS  Article  Google Scholar 

  • Olson, W.A.; Dayton, P.G.; Israili, Z.H. and Pruitt, A.W.: Spectrophotofluorometric assay for isoniazid and acetylisoniazid in plasma adapted to pediatric studies. Clinical Chemistry 23: 745–748 (1977).

    PubMed  CAS  Google Scholar 

  • Olson, W.; Miceli, J. and Weber, W.: Dose-dependent changes in sulfamethazine kinetics in rapid and slow isoniazid acetylators. Clinical Pharmacology and Therapeutics 23: 204–211 (1978).

    PubMed  CAS  Google Scholar 

  • Peters, J.H.; Miller, K.S. and Brown, P.: Studies on the metabolic basis for the genetically determined capacities for isoniazid inactivation in man. Journal of Pharmacology and Experimental Therapeutics 150: 298–304 (1965).

    PubMed  CAS  Google Scholar 

  • Peters, J.H.; Gordon, R.G.; Ghoul, D.L.; Tolentino, J.G.; Walsh, G.P. and Levy, L.: The disposition of the antileprotic drug dapsone in Philippine subjects. American Journal of Tropical Medicine and Hygiene 21: 450–457 (1972).

    PubMed  CAS  Google Scholar 

  • Peters, J.H.; Shepard, C.C.; Gordon, G.R.; Rojas, A.V. and Elizondo, D.S.: The incidence of DDS resistance in lepromatous patients in Costa Rica: Their metabolic disposition of DDS. International Journal of Leprosy 44: 143–151 (1976).

    CAS  Google Scholar 

  • Public Health Service, U.S. Department of Health, Education and Welfare: Isoniazid-associated hepatitis: Summary of the report of the tuberculosis committee and special consultants to the director. Center for Disease Control, Morbidity and Mortality 23: 97–98 (1974).

    Google Scholar 

  • Rao, K.V.N.; Mitchison, D.A.; Nair, N.G.K.; Prema, K. and Tripathy, S.P.: Sulphadimidine acetylation test for classification of patients as slow or rapid inactivators of isoniazid. British Medical Journal 3: 495–497 (1970).

    PubMed  CAS  Article  Google Scholar 

  • Rao, K.V.N.; Kailasam, S.; Menon, N.K. and Radharrishna, S.: Inactivation of isoniazid by condensation in a syrup preparation. Indian Journal of Medical Research 50: 1343–1353 (1971).

    Google Scholar 

  • Reidenberg, M.M.: Obesity and fasting effects on drug metabolism and drug action in man. Clinical Pharmacology and Therapeutics 22: 729–734 (1977).

    PubMed  CAS  Google Scholar 

  • Reidenberg, M.M.; Shear, L. and Cohen, R.V.: Elimination of isoniazid in patients with impaired renal function. American Review of Respiratory Diseases 108: 1426–1428 (1973).

    CAS  Google Scholar 

  • Robson, J.M. and Sullivan, F.M.: Antituberculosis drugs. Pharmacological Reviews 15: 169–223 (1963).

    PubMed  CAS  Google Scholar 

  • Rosenthal, A.R.; Self, T.H.; Baker, E.D. and Linden, R.A.: Interaction of isoniazid and warfarin. Journal of the American Medical Association 238: 2177 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Salako, L.A. and Aderounmu, A.F.: Determination of the isoniazid acetylator phenotype in a West African population. Tubercle 58: 109–112 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Sarma, G.R.; Kailasam, S.; Mitchison, D.A.; Nair, N.G.K.; Radhakrishna, S. and Tripathy, S.P.: Studies of serial plasma isoniazid concentrations with different doses of a slow-release preparation of isoniazid. Tubercle 56: 314–322 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Saxena, S.J.; Stewart, J.T.; Honigberg, I.L.; Washington, J.G. and Keene, G.R.: Liquid chromatography in pharmaceutical analyses VIII: Determination of isoniazid and acetyl derivative. Journal of Pharmaceutical Sciences 66: 83–86 (1977).

    Google Scholar 

  • Scheinhorn, D.J. and Angelillo, V.A.: Antituberculous therapy in pregnancy. Risks to the fetus. Western Journal of Medicine 127: 195–198 (1977).

    PubMed  CAS  Google Scholar 

  • Schloot, W.; Blume, K.G.; Goedde, H.W.; Flatz, G. and Bhaibulay, A.: Human Genetics 4: 274–279 (1967).

    PubMed  CAS  Article  Google Scholar 

  • Schmeidel, A.: The problem of rapid isoniazid inactivation. Bulletin of the International Union Against Tuberculosis 32: 508–512 (1962).

    Google Scholar 

  • Schmidt, L.H.: The problem of the rapid inactivator. Bulletin of the International Union Against Tuberculosis 32: 487–502 (1962).

    Google Scholar 

  • Schneck, D.W.; Sprouse, J.S.; Shiroff, R.A.; Vary, J.E.; DeWitt, F.O. and Hayes, A.H.: Effect of coadministration of procainamide and isoniazid on each other’s acetylation pathway. Pharmacology 18: 34–41 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Schroeder, H.: Simplified method for determining acetylator phenotype. British Medical Journal 3: 506–507 (1972).

    Article  Google Scholar 

  • Schroeder, H. and Evans, D.A.P.: The polymorphic acetylation of sulphapyridine in man. Journal of Medical Genetics 9: 168–171 (1972).

    Article  Google Scholar 

  • Schulte, E.H.; Schloot, W. and Goedde, H.W.: Purification of human liver serotonin/isoniazid N-acetyltransferase by preparative polyacetylamide-electrophoresis and determination of molecular weight. Zeitschrift fuer Naturforschung 29: 661–666 (1974).

    CAS  Google Scholar 

  • Schwenk, R.; Kelly, K.; Tse, K.S. and Sehon, A.H.: Radioimmunoassay for isoniazid. Clinical Chemistry 21: 1059–1062 (1975).

    PubMed  CAS  Google Scholar 

  • Scott, E.M.; Wright, R.C. and Weaver, D.D.: The discrimination of phenotypes for rate of disappearance of isonicotinoyl hydrazide from serum. Journal of Clinical Investigation 48: 1173–1176 (1969).

    PubMed  CAS  Article  Google Scholar 

  • Smith, F.W.; Catto, G.R.D. and MacLeod, M.: Treatment of pulmonary tuberculosis in a patient on maintenance hemodialysis. Postgraduate Medical Journal 50: 478–481 (1974).

    PubMed  CAS  Article  Google Scholar 

  • Smith, J.; Tyrrell, W.F.; Gow, A.; Allan, G.W. and Lees, A.W.: Hepatotoxicity in rifampin-isoniazid treated patients related to their rate of isoniazid inactivation. Chest 61: 587–588 (1972).

    PubMed  CAS  Article  Google Scholar 

  • Smith, S.E. and Kyi, T.: Inactivation of isoniazid in Burmese subjects. Nature 217: 1273 (1968).

    PubMed  CAS  Article  Google Scholar 

  • Spyridis, P.; Sinaniotis, C.; Papadea, I.; Oreopoulos, L.; Hadjiyiannis, S. and Papadatos, C.: Isoniazid liver injury during chemoprophylaxes in children. Archives of Disease in Childhood 54: 65–67 (1979).

    PubMed  CAS  Article  Google Scholar 

  • Sunahara, S.; Vrano, M.; Lin, H.T.; Cheg, T.J. and Jarumilinda, A.: Further observations on trimodality of frequency distribution curve of biologically active isoniazid blood levels and ‘cline’ in frequencies of alleles controlling isoniazid inactivation. Acta Tuberculosa et Pneumologica Scandinavica 43: 181–195 (1963).

    CAS  Google Scholar 

  • Sunahara, S.; Vrano, M. and Ogawa, M.: Genetical and geographic studies on isoniazid inactivation. Science 134: 1530–1531 (1960).

    Article  Google Scholar 

  • Sutton, G. and Kupferberg, H.J.: Isoniazid as an inhibitor of primidone metabolism. Neurology 25: 1179–1181 (1975).

    PubMed  CAS  Article  Google Scholar 

  • Sved, S.; McGilveray, I.J. and Beaudoin, N.: Bioavailability of three isoniazid formulations. Journal of Pharmaceutical Sciences 66: 1761–1764 (1977).

    PubMed  CAS  Article  Google Scholar 

  • Szeinberg, A.; Baror, R. and Sheba, C.: Distribution of isoniazid inactivator types; in Goldschmidt (Ed) The Genetics of Migrant and Isolate Populations p.279 (Williams and Wilkins, New York 1963).

    Google Scholar 

  • Tiitinen, H.: Isoniazid and ethionamide serum levels and inactivation in Finnish subjects. Scandinavian Journal of Respiratory Diseases 50: 110–124 (1969).

    PubMed  CAS  Google Scholar 

  • Tiitinen, H. and Mattila, M.J.: Experiments on drug elimination in tuberculosis patients. Scandinavian Journal of Clinical and Laboratory Investigation 21 (Suppl. 101): 87–88 (1968).

    Google Scholar 

  • Tiitinen, H.; Mattila, M.J. and Eriksson, A.W.: Comparison of the isoniazid inactivation in Finns and Lapps. Annales Medicinae Internae Fenniae 57: 161–166 (1968).

    PubMed  CAS  Google Scholar 

  • Timbrell, J.A.; Wright, J.M. and Baillie, T.A.: Monoacetylhydrazine as a metabolite of isoniazid in man. Clinical Pharmacology and Therapeutics 22: 602–608 (1977).

    PubMed  CAS  Google Scholar 

  • Tuberculosis Chemotherapy Centre, Madras: A controlled comparison of a twice-weekly and three once-weekly regimens in the initial treatment of pulmonary tuberculosis. Bulletin of the World Health Organization 43: 143–206 (1970).

    Google Scholar 

  • Tuberculosis Chemotherapy Centre, Madras: A controlled comparison of two fully supervised once-weekly regimens in the treatment of newly diagnosed pulmonary tuberculosis. Tubercle 54: 23–45 (1973).

    Article  Google Scholar 

  • Varughese, P.; Hamilton, E.J. and Eidus, L.: Mass phenotyping of isoniazid inactivators by automated determination of acetyl isoniazid in urine. Clinical Chemistry 20: 639–641 (1974).

    PubMed  CAS  Google Scholar 

  • Viznerova, A.; Slavikova, Z. and Ellard, G.A.: The determination of the acetylator phenotype of the tuberculosis patients in Czechoslovakia using sulphadimidine. Tubercle 54: 67–72 (1973).

    PubMed  CAS  Article  Google Scholar 

  • Walstad, R.A.: In aktivisering au medikamenter ved acetylering. Tidsskrift for Den Norsks Laegeforening 2: 100–103 (1975).

    Google Scholar 

  • Weber, W.W.: Acetylation of drugs; in Fishman (Ed) Metabolic Conjugation and Metabolic Hydrolysis, pp.249–296 (Academic Press, New York 1973).

    Google Scholar 

  • Weber, W.W. and Brenner, W.: A filter paper method for determining isoniazid acetylator phenotype. American Journal of Human Genetics 26: 467–473 (1974).

    PubMed  CAS  Google Scholar 

  • Weber, W.W. and Glowinski, I.B.: Acetylation; in Jakoby (Ed) Enzymatic Basis for Detoxification (Academic Press, New York, in press 1979).

    Google Scholar 

  • Weber, W.W.; Hein, D.W.; Hirata, M. and Patterson, E.: Genetics of drug acetylation: Molecular nature of the INH acetylation polymorphism; in Aitio (Ed) Conjugation Reactions in Drug Biotransformation, pp. 145–153 (Elsevier/North-Holland Biomedical Press, Amsterdam 1978).

    Google Scholar 

  • Weber, W.W.; Radtke, H.E. and Tannen, R.H.: Extra-hepatic N-acetyltransferases and N-deacetylases; in Gram (Ed) Extrahepatic Metabolism of Drugs and Other Foreign Compounds (Spectrum Publications. Jamaica, New Yurk. in press 1979).

    Google Scholar 

  • Welles, J.S.; Anderson, R.C. and Chen, K.K.: Isoniazid distribution in body fluids of the dog and rabbit. Proceedings of the Society for Experimental Biology and Medicine, New York 84: 726–728 (1953).

    CAS  Google Scholar 

  • Wiesel, L.L.: Investigation of the synergism of isonicotinic acid hydrazide and cortisone I. Effect of isonicotinic acid on the metabolism of cortisone by liver tissue. American Journal of the Medical Sciences 232: 412–414 (1956).

    PubMed  CAS  Article  Google Scholar 

  • Wiesel, L.L.; Barritt, A.S. and Scheid, C.J.: Investigation of the synergism of isonicotinic acid hydrazide and cortisone II. Long term study of the synergistic action of isonicotinic acid hydrazide and cortisone acetate in the treatment of rheumatoid arthritis. American Journal of the Medical Sciences 232: 415–418 (1956).

    PubMed  CAS  Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Weber, W.W., Hein, D.W. Clinical Pharmacokinetics of Isoniazid. Clin Pharmacokinet 4, 401–422 (1979). https://doi.org/10.2165/00003088-197904060-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-197904060-00001

Keywords

  • Isoniazid
  • Clinical Pharmacokinetic
  • Slow Acetylators
  • American Review
  • Isonicotinic Acid