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Increased hepatic cytochrome P4503A activity decreases the risk of developing steroid-induced osteonecrosis in a rabbit model by Toshiaki Masada; Kentaro Iwakiri; Yutaka Oda; Yasunori Kaneshiro; Hiroyoshi Iwaki; Hirotsugu Ohashi; Kunio Takaoka is a Medicine article available to read on EtoBox.

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## Abstract Low hepatic cytochrome P4503A (CYP3A) activities might play an important role for inducing osteonecrosis of the femoral head (ONFH) by corticosteroids. However, the relationship between hepatic CYP3A activity and steroid‐induced ONFH is unknown. We have examined the relationship between hepatic CYP3A activity and the inducibility of ONFH in a rabbit model. Sixty rabbits were divided into three groups. Hepatic CYP3A inducer (phenobarbital, group P; __n__ = 15), inhibitor (itraconazole, group I; __n__ = 15), or saline (group C, __n__ = 30) was administrated for 3 weeks before intramuscular methylprednisolone. In groups P and I, hepatic CYP3A levels were measured by midazolam clearance before treatment (baseline) and before methylprednisolone injection. All animals were sacrificed 3 weeks after methylprednisolone injection and both femurs were harvested and examined histologically for osteonecrosis. Midazolam clearance was significantly increased and decreased, compared with baseline in groups P and I respectively (__p__ < 0.0005, __p__ < 0.002). The incidence of osteonecrosis in group P (33%) was significantly lower than in group I (100%) and group C (83%; __p__ < 0.001 f

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Author

Toshiaki Masada; Kentaro Iwakiri; Yutaka Oda; Yasunori Kaneshiro; Hiroyoshi Iwaki; Hirotsugu Ohashi; Kunio Takaoka

Publisher

Elsevier Science; Wiley (John Wiley & Sons); Wiley-Blackwell; Wiley (ISSN 0736-0266)

Published

2007

Language

EN

Field

Medicine (Health Sciences)