title: Effects of repeated administration of rifampicin and isoniazid on vitamin D metabolism in mice.
abstract: Vitamin D deficiency is prevalent in tuberculosis (TB) patients and the anti-TB drugs, especially rifampicin (RIF) and isoniazid (INH), are associated with altered endocrine actions of vitamin D. Although it is well-known that these two drugs can affect a variety of cytochrome P450 (CYP450) activity, their influence on the CYP450 enzymes involved in vitamin D metabolism remains largely unknown. To fill this critical gap, serum vitamin D status and the expression of hepatic CYP2R1 and CYP27A1 and renal CYP27B1 and CYP24A1 were assessed in mice following 3-week exposure to 100 mg/kg/day RIF or (and) 50 mg/kg/day INH. Unexpectedly, we found either RIF or co-treatment the two drugs increased the concentrations of 25-hydroxyvitamin D3 (25(OH)D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), without affecting 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) status. In parallel, enhanced hepatic expressions of 25-hydroxylase enzymes, CYP2R1 and (or) CYP27A1, were found in RIF and RIF+INH groups. However, co-administration of RIF and INH inhibited the expression of CYP27B1, while inducing CYP24A1 expression. Collectively, our data firstly showed that RIF and co-treatment of RIF and INH can both enhance 25-hydroxylation and 24-hydroxylation of vitamin D, providing novel evidence for the involvement of anti-TB drugs in the metabolism of vitamin D.
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410010, China.
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410010, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410010, China.
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410010, China.
authors.forename: Yungui
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410010, China. Electronic address: lihuande1953@126.com.
authors.forename: Huande
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410010, China.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410010, China; Department of Pharmacy, Jining First People's Hospital, Jining Medical University, Jining 272000, China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Dang
authors.affiliation: Institute of Clinical Pharmacy & Pharmacology, Second Xiangya Hospital, Central South University, Changsha 410010, China.
authors.forename: Mimi
authors.initials: M
authors.lastname: Tang
authors.affiliation: Department of Pharmacy, Jining First People's Hospital, Jining Medical University, Jining 272000, China. Electronic address: jpoet89@126.com.
authors.forename: Pei
authors.initials: P
authors.lastname: Jiang
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000037:antagonists & inhibitors / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007538:Isoniazid / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D012293:Rifampin / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D000995:Antitubercular Agents; D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D007538:Isoniazid; D012293:Rifampin
keywords: Isoniazid; Rifampicin; Tuberculosis; Vitamin D metabolism