02457nas a2200325   4500000000100000008004100001260000900042653001000051653002600061653004400087653002800131653001400159653004100173653003000214653002200244653001100266653000900277653001400286653001300300653001700313100001600330700002000346700002000366700002100386245010600407300001100513490000700524520158600531022001402117       2003                            d  c200310aAdult10aAnti-Bacterial Agents10aAnti-Inflammatory Agents, Non-Steroidal10aBiological Availability10aCelecoxib10aChromatography, High Pressure Liquid10aCyclooxygenase Inhibitors10aDrug Interactions10aHumans10aMale10aPyrazoles10aRifampin10aSulfonamides1 aJayasagar G1 aKrishna Kumar M1 aChandrasekhar K1 aMadhusudan Rao Y00aInfluence of rifampicin pretreatment on the pharmacokinetics of celecoxib in healthy male volunteers.  a287-950 v193 a<p>The effect of rifampicin pretreatment on the pharmacokinetics of celecoxib was investigated in 12 healthy male human volunteers. After an overnight fast, celecoxib 200 mg was administered to the volunteers, either alone or after 5 days pretreatment with once daily dose of 600 mg rifampicin. Serum concentrations of celecoxib were estimated by reverse phase HPLC. Pharmacokinetic parameters were determined based on non-compartmental model analysis using the computer program KINETICA. A significant difference was observed in AUC(0-1) (4531.28 +/- 2147 vs 1629.1 +/- 1006 ng x h x ml(-1), p < 0.0001), AUC(0-infinity) (4632.42 +/- 2221.75 vs 1629.46 +/- 1012.61 ng x h x ml(-1), p = 0.0006), Cmax (544.89 +/- 273.91 vs 238.61 +/- 146.34 ng/ml, p = 0.04), t(1/2) (9.3 +/- 3.58 vs 4.0 +/- 1.43 h, p = 0.0317) and Cl/f (43.14 +/- 36.23 vs 122.85 +/- 95 l x h(-1), p < 0.0001) of celecoxib administered before and after rifampicin pretreatment. However, time to reach peak concentration, tmax (4 +/- 0.88 vs 4 +/- 0.83 h) and volume of distribution Vd/f (583 +/- 251 vs 710 +/- 690 l/kg) were not affected significantly. Rifampicin pretreatment reduced the AUC of celecoxib by 64% and increased the clearance by 185%. This may be due to increased metabolism of celecoxib due to the induction of cytochrome P4502C9 (CYP2C9) in liver. This interaction has a significant clinical relevance and may warrant dosage adjustment when celecoxib is co-administered with rifampicin in chronic treatment conditions, such as tuberculosis, leprosy and other infections of joints, bones, etc.</p>  a0792-5077