Effect of isoniazid on vitamin D metabolism and hepatic monooxygenase activity

isoniazid, 300 mg daily for 14 days, reduced serum calcium and phosphate levels (P less than 0.001) in eight healthy subjects. After a single dose of isoniazid the concentration of 1 alpha-,25-dihydroxyvitamin D, the most active metabolite of vitamin D, fell by 47% (P less than 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 less than 0.01). Parathyroid hormone levels rose by 36% (P less than 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 1 alpha-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.