Some pharmacokinetic properties and bioavailability by oral and rectal route of piroxicam in rodents and in man

Abstract

In a comparative study on rodents and on man the fundamental pharmacokinetic properties of 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (piroxicam) were assessed and the bioavailability of the drug after oral and rectal administration was determined. It was found that: the plasma half-life is much longer in man (ca. 35 h) than in rodents (3--5.5 h in the rabbit, 5 h in the rat and mouse). The long plasma disappearance time in man is attributed to the relatively strong binding with the plasma proteins. A thorough pharmacokinetic analysis in the rabbit revealed a two-compartment distribution of the drug with an intercompartmental t 1/2 0.67 h and an excretion + metabolisation t 1/2 of 3.16 h. The extremely low excretion of the drug as such or as the glucuronide in the bile and urine suggests that the main excretion route is metabolic. The rectal bioavailability is similar to the oral bioavailability both in rabbit and rat and in man. Comparison of the AUC after i.v. injection with the AUCs after oral and rectal administration in the rabbit seems to show that absorption by rectal and oral route is quantitative.