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Effect of isoniazid on vitamin D metabolism and hepatic monooxygenase activity
Author(s) -
Brodie Martin J,
Boobis Alan R,
Hillyard Carmel J,
Abeyasekera Gamini,
Maclntyre Ian,
Park B Kevin
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.173
Subject(s) - isoniazid , rifampicin , medicine , endocrinology , metabolite , chemistry , vitamin d and neurology , active metabolite , vitamin , metabolism , parathyroid hormone , drug metabolism , pharmacology , calcium , biochemistry , tuberculosis , antibiotics , pathology
Isoniazid, 300 mg daily for 14 days, reduced serum calcium and phosphate levels (P < 0.001) in eight healthy subjects. After a single dose of isoniazid the concentration of 1α‐,25‐dihydroxyvitamin D, the most active metabolite of vitamin D, fell by 47% (P < 0.01) and was reduced throughout the study. Levels of 25‐hydroxyvitamin D, the major circulating form of the vitamin, declined in all subjects and to below normal range in six (P < 0.01). Parathyroid hormone levels rose by 36% (P < 0.01) in response to the relative hypocalcemia produced. Isoniazid inhibited hepatic mixed‐function oxidase activity, as evidenced by a reduction in antipyrine and cortisol oxidation, and a similar inhibition of the hepatic 25‐hydroxylase and renal 1α‐hydroxylase would explain the reduction in the corresponding vitamin D metabolites. This perturbation of vitamin D metabolism differs from the vitamin D wasting effects after rifampicin. Patients with tuberculosis treated with isoniazid and rifampicin may show changes similar to those shown here in calcium and phosphate homeostasis and thus may be at risk of developing metabolic bone disorders. Clinical Pharmacology and Therapeutics (1981) 30 , 363–367; doi: 10.1038/clpt.1981.173