rifampin has been researched along with Osteomalacia* in 7 studies
7 other study(ies) available for rifampin and Osteomalacia
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Enhancement of hepatic 4-hydroxylation of 25-hydroxyvitamin D3 through CYP3A4 induction in vitro and in vivo: implications for drug-induced osteomalacia.
Long-term therapy with certain drugs, especially cytochrome P450 (P450; CYP)-inducing agents, confers an increased risk of osteomalacia that is attributed to vitamin D deficiency. Human CYP24A1, CYP3A4, and CYP27B1 catalyze the inactivation and activation of vitamin D and have been implicated in the adverse drug response. In this study, the inducibility of these enzymes and monohydroxylation of 25-hydroxyvitamin D3 (25OHD3) were evaluated after exposure to P450-inducing drugs. With human hepatocytes, treatment with phenobarbital, hyperforin, carbamazepine, and rifampin significantly increased the levels of CYP3A4, but not CYP24A1 or CYP27B1 mRNA. In addition, rifampin pretreatment resulted in an 8-fold increase in formation of the major metabolite of 25OHD3, 4β,25(OH)2D3. This inductive effect was blocked by the addition of 6',7'-dihydroxybergamottin, a selective CYP3A4 inhibitor. With human renal proximal tubular HK-2 cells, treatment with the same inducers did not alter CYP3A4, CYP24A1, or CYP27B1 expression. 24R,25(OH)2 D3 was the predominant monohydroxy metabolite produced from 25OHD3, but its formation was unaffected by the inducers. With healthy volunteers, the mean plasma concentration of 4β,25(OH)2D3 was increased 60% (p < 0.01) after short-term rifampin administration. This was accompanied by a statistically significant reduction in plasma 1α,25(OH)2D3 (-10%; p = 0.03), and a nonsignificant change in 24R,25(OH)2D3 (-8%; p = 0.09) levels. Further analysis revealed a negative correlation between the increase in 4β,25(OH)2D3 and decrease in 1α,25(OH)2D3 levels. Examination of the plasma monohydroxy metabolite/25OHD3 ratios indicated selective induction of the CYP3A4-dependent 4β-hydroxylation pathway of 25OHD3 elimination. These results suggest that induction of hepatic CYP3A4 may be important in the etiology of drug-induced osteomalacia. Topics: Adult; Calcifediol; Cell Line; Cytochrome P-450 CYP3A; Enzyme Induction; Female; Humans; Hydroxylation; Liver; Male; Middle Aged; Osteomalacia; Rifampin; Young Adult | 2013 |
Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia.
Vitamin D controls calcium homeostasis and the development and maintenance of bones through vitamin D receptor activation. Prolonged therapy with rifampicin or phenobarbital has been shown to cause vitamin D deficiency or osteomalacia, particularly in patients with marginal vitamin D stores. However, the molecular mechanism of this process is unknown. Here we show that these drugs lead to the upregulation of 25-hydroxyvitamin D(3)-24-hydroxylase (CYP24) gene expression through the activation of the nuclear receptor pregnane X receptor (PXR; NR1I2). CYP24 is a mitochondrial enzyme responsible for inactivating vitamin D metabolites. CYP24 mRNA is upregulated in vivo in mice by pregnenolone 16alpha-carbonitrile and dexamethasone, 2 murine PXR agonists, and in vitro in human hepatocytes by rifampicin and hyperforin, 2 human PXR agonists. Moreover, rifampicin increased 24-hydroxylase activity in these cells, while, in vivo in mice, pregnenolone 16alpha-carbonitrile increased the plasma concentration of 24,25-dihydroxyvitamin D(3). Transfection of PXR in human embryonic kidney cells resulted in rifampicin-mediated induction of CYP24 mRNA. Analysis of the human CYP24 promoter showed that PXR transactivates the sequence between -326 and -142. We demonstrated that PXR binds to and transactivates the 2 proximal vitamin D-responsive elements of the human CYP24 promoter. These data suggest that xenobiotics and drugs can modulate CYP24 gene expression and alter vitamin D(3) hormonal activity and calcium homeostasis through the activation of PXR. Topics: Animals; Cells, Cultured; Cytochrome P-450 Enzyme System; Gene Expression Regulation; Hepatocytes; Humans; Mice; Molecular Sequence Data; Mutation; Osteomalacia; Pregnane X Receptor; Promoter Regions, Genetic; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Rifampin; RNA, Messenger; Steroid Hydroxylases; Transcriptional Activation; Vitamin D Response Element; Vitamin D3 24-Hydroxylase | 2005 |
Osteomalacia during rifampicin and isoniazid therapy is rare in Hong Kong.
Prolonged therapy with rifampicin and isoniazid can cause vitamin D deficiency or osteomalacia, particularly in patients with marginal vitamin D stores. In the New Territories East of Hong Kong, there were at least 1,526 new cases of tuberculosis over a 14-month period in 1994-1995. Any severe cases of osteomalacia were expected to be hospitalized in the sole general teaching hospital of the region. However, among all the general medical patients with one of their discharge ICD codes being 268 (vitamin D deficiency) or 275 (disorders of mineral metabolism), none had osteomalacia due to rifampicin and isoniazid chemotherapy. Thus, this complication appears to be rare in Hong Kong whose residents generally have a higher vitamin D status than those of the U.K. Topics: Antitubercular Agents; Hong Kong; Hospitals, Teaching; Humans; Isoniazid; Osteomalacia; Rifampin; Tuberculosis | 1996 |
[Rifampicin, vitamin K and osteomalacia].
Topics: Humans; Osteomalacia; Rifampin; Vitamin K | 1986 |
Calcium metabolism during rifampicin and isoniazid therapy for tuberculosis.
Calcium metabolism was studied in 83 patients during eighteen months' rifampicin and isoniazid therapy for tuberculosis by measurements including calcium, alkaline phosphatase and 25-hydroxycholecalciferol (25-HCC). Five out of 52 Indian patients in the series were found to have osteomalacia, a prevalence probably no higher than in the Asian population in the UK at large. Moreover, osteomalacia responded to physiological supplementation with vitamin D. One European out of 31 had osteomalacia due to low vitamin D intake. Serum calcium was compared in 17 patients before and after six months of antituberculous chemotherapy but no significant difference was detected (P greater than 0.1). Two Indian patients were in positive calcium balance with low to normal plasma 25-HCC levels, indicating that an effect on 1,25 dihydroxyvitamin D activity during therapy was unlikely. It is concluded that rifampicin when combined with isoniazid has no significant effect on calcium metabolism over an eighteen-month treatment period. Topics: Adolescent; Adult; Calcium; Drug Therapy, Combination; Female; Humans; Isoniazid; Male; Middle Aged; Osteomalacia; Rifampin; Tuberculosis; Vitamin D | 1982 |
Rifampicin induced osteomalacia.
Topics: Adult; Female; Humans; Osteomalacia; Rifampin; Tuberculosis, Lymph Node | 1981 |
Rifampicin and vitamin D metabolism.
A 2-wk course of rifampicin orally (600 mg/day) in 8 male subjects resulted in a consistent fall in plasma 25-hydroxycholecalciferol (25-OHD) levels of around 70%, accompanied by increased oxidation of antipyrine and 6 beta-hydroxycortisol (indicative of hepatic enzyme induction). Plasma levels of 1,25-dihydroxycholecalciferol, parathyroid hormone, and calcitonin were not altered. The fall in 25-OHD may represent the earliest lesion of drug-induced osteomalacia. Topics: Adult; Calcium; Enzyme Induction; Humans; Hydroxycholecalciferols; Male; Mixed Function Oxygenases; Osteomalacia; Parathyroid Hormone; Rifampin; Time Factors; Vitamin D | 1980 |