title: Effects of dose and sex on the pharmacokinetics of piroxicam in the rat.
abstract: The effects of dose and sex on the pharmacokinetics of piroxicam were studied in the rat. Piroxicam was administered intravenously at doses of 0.50 and 5.0 mg kg-1 to male and female rats. Plasma drug concentrations were determined by a highly sensitive high-performance liquid chromatographic technique. Non-compartmental pharmacokinetic parameters were calculated by area/moment analysis. A prolonged terminal half-life averaging 13.3 h in male rats and 40.8 h in female rats was observed. Dose had no effect on the disposition of piroxicam. The sex of the rat, however, had a marked effect on piroxicam pharmacokinetics, with mean total clearance differing three-fold from 0.0184 l h-1 kg-1 in male rats to 0.00622 l h-1 kg-1 in female rats. The free fraction of piroxicam in serum was greater in male rats than in female rats owing to a higher association constant for piroxicam binding to female rat serum proteins. Free piroxicam clearance differed approximately two-fold with mean values of 0.764 l h-1 kg-1 and 0.418 l h-1 kg-1 in male and female rats, respectively. Thus, protein binding partially explained the sex-dependent disposition of piroxicam. However, sex-dependent metabolism of the drug also appears to be a major determinant of sex-related differences in piroxicam pharmacokinetics. Steady-state volume of distribution was unaffected by sex. Half-life and mean residence time were three-fold greater in female rats owing to the three-fold lower clearance value compared to male rats.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens 30602.
authors.forename: L K
authors.initials: LK
authors.lastname: Roskos
authors.forename: F D
authors.initials: FD
authors.lastname: Boudinot
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D010894:Piroxicam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D012737:Sex Factors
chemical_list: D010894:Piroxicam