Bioavailability of diclofenac sodium after pretreatment with diosmin in healthy volunteers.
Diclofenac sodium is a non-steroidal anti-inflammatory drug (NSAID). It undergoes extensive Phase I and Phase II metabolism and in vitro it is a specific CYP2C9 substrate. The first part of the study consisted of oral administration of 100 mg of diclofenac sodium (Voveran100) to 12 healthy male volunteers. Blood samples were collected from the antecubital vein at intervals of 0, 0.5, 1, 2, 3, 4, 5, 6, 7, and 8 hours. The second part of the study was conducted after a washout period of 7 days. Treatment with 500 mg p.o. of diosmin (Venex 500) was given daily for 9 days. On day 10, 100 mg of diclofenac sodium (Voveran 100) was administered. Blood samples were obtained as mentioned earlier and pharmacokinetic parameters of diclofenac before and after pretreatment with diosmin analyzed by HPLC. Diosmin pretreatment significantly enhanced AUC, C(max) and t1/2 with a concomitant reduction in CL/f. Diosmin might have inhibited the microsomal CYP2C9 mediated oxidation of diclofenac sodium.
Rajnarayana
K
K
Department of Pharmacology and Clinical Pharmacy, University College of Pharmaceutical Sciences, Kakatiya University, Warangal - 506 009, AP, India.
Venkatesham
A
A
Krishna
Devarakonda R
DR
D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001682:Biological Availability; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects; D004008:Diclofenac / Q000097:blood / Q000493:pharmacokinetics*; D004145:Diosmin / Q000097:blood / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D008297:Male
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D004145:Diosmin; D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases