Effect of rifampicin and isoniazid on vitamin D metabolism

MJ Brodie, AR Boobis, CJ Hillyard… - Clinical …, 1982 - Wiley Online Library
MJ Brodie, AR Boobis, CJ Hillyard, G Abeyasekera, JC Stevenson, I MacIntyre, BK Park
Clinical Pharmacology & Therapeutics, 1982Wiley Online Library
Rifampicin, 600 mg, and isoniazid, 300 mg daily for 14 days, reduced circulating levels of 25‐
hydroxy vitamin D (25‐OHD) and 1α, 25‐dihydroxy vitamin D (1, 25 (OH) 2D) by 34%(P<
0.01) and 23%(P< 0.05) in eight healthy subjects. This was accompanied by a rise in
parathyroid hormone (PTH) of 57%(P< 0.01), but not by a fall in serum calcium or phosphate
levels. There was induction of endogenous cortisol oxidation in all subjects, but only in four
fast acetylators was there a concomitant increase in antipyrine elimination. In the four slow …
Rifampicin, 600 mg, and isoniazid, 300 mg daily for 14 days, reduced circulating levels of 25‐hydroxy vitamin D (25‐OHD) and 1α, 25‐dihydroxy vitamin D (1,25(OH)2D) by 34% (P < 0.01) and 23% (P < 0.05) in eight healthy subjects. This was accompanied by a rise in parathyroid hormone (PTH) of 57% (P < 0.01), but not by a fall in serum calcium or phosphate levels. There was induction of endogenous cortisol oxidation in all subjects, but only in four fast acetylators was there a concomitant increase in antipyrine elimination. In the four slow acetylators antipyrine metabolism was inhibited after the first dose of the drugs. In nine tuberculous patients followed serially there was a fall in 25‐OHD and 1,25 (OH)2D and a rise in PTH at the end of 1 mo (P < 0.05). After 6 mo therapy 25‐OHD concentration was further reduced (P < 0.01), but there was now no significant change in 1,25 (OH)2D or PTH levels. Combination treatment with rifampicin and isoniazid perturbs vitamin D metabolism, but less than might have been predicted from reports on each drug given alone. Nevertheless, tuberculous patients with already compromised calcium homeostasis receiving this combination of drugs should be carefully monitored.
Clinical Pharmacology and Therapeutics (1982) 32, 525–530; doi:10.1038/clpt.1982.197
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