Experimental Study Of The Effects Of P-gp Activity Modulated By Rifampicin On The Steroid Induced Osteonecrosis Of Femoral Head

Objective:1. To observe regulatory effects of different routes of rifampicin administration on P-glycoprotein (P-gp) and hepatic cytochrome P450 (Cyp450) in rabbits.2. To study effects of different routes of rifampicin administration on steroid induced necrosis of femoral head.Method:32 rabbits were equally divided into 4 groups according to different methods of rifampicin administration for one week, which were oral, intramuscular injection, local implantation, and normal saline only, respectively. Single dose of steroid was injected intramuscularly on the 8th day.4 weeks later, activity of peripheral P-gp, bone marrow P-gp and hepatic Cyp450 were observed, as well as some specific serological indicators on osteogenic and osteoclastic activity. Area of trabecular bone, fat vacuoles amount, fat cell diameter and empty osteocyte lacunaes amount were analyzed from HE staining pathologic sections of femoral head.Result:1. Compared to model group, peripheral P-gp activity and hepatic Cyp450 could be up-regulated by either oral administration or intramuscular injection of rifampicin. Local implantation of the drug increases P-gp activity only in femoral head. No change of peripheral P-gp or hepatic Cyp450 is noticed in local implanted cases.2. Oral administration of rifampicin could increase Osteogenic indicators (Osteocalcin, Alkaline phosphatase) in serum and decrease osteoclastic indicators(Tartrate resistant acid phosphatase). Local implantation of the drug has no effect on these serological indicators.3. Compared to model group, cases treated by oral administration, intramuscular injection and Local implantation of rifampicin have larger area of trabecular bone, less fat vacuoles and less empty osteocyte lacunaes on pathological sections.Conclusion:Peripheral P-gp activity and hepatic Cyp450 could be up-regulated by either oral administration or intramuscular injection of rifampicin; Local implantation of rifampicin could increase P-gp activity in femoral head but has no effect on peripheral P-gp activity or hepatic Cyp450; Bone loss could be restrained by all three different ways of rifampicin administration.