ORAL BIOAVAILABILITY OF CHF1194, AN INCLUSION COMPLEX OF PIROXICAM AND BETA-CYCLODEXTRIN, IN HEALTHY-SUBJECTS UNDER SINGLE-DOSE AND STEADY-STATE CONDITIONS

CHF1194 is an inclusion complex of beta-cyclodextrin with the nonstero idal anti-inflammatory drug piroxicam. In man, beta-cyclodextrin acts as a carrier of piroxicam. As the inclusion complex of piroxicam-beta- cyclodextrin is wettable and more water soluble, the absorption rate o f the drug is increased whilst its other pharmacokinetic characteristi cs remain unchanged. The aim of the present study in 12 healthy subjec ts was to compare the oral bioavailability of 20 mg piroxicam in a CHF 1194 tablet and a plain piroxicam capsule after a single dose and afte r two weeks of once daily administration, and also to assess the plasm a levels and urinary excretion of beta-cyclodextrin after CHF1194 admi nistration. The two treatments were administered in cross-over fashion , separated by a wash-out period of three weeks. Piroxicam, 5'-hydroxy piroxicam and beta-cyclodextrin were monitored in plasma and urine for 120 h after the first and last doses. Clinical tolerance was excellen t and no adverse event occurred during either phase of the study. The extent of absorption of piroxicam from the CHF1194 tablet after the si ngle dose was equivalent to that after the plain piroxicam capsule, wi thin confidence limits of less than 80-125%. After repeated dosing, CH F1194 yielded the same steady-state systemic concentrations of piroxic am and 5'hydroxypiroxicam as the reference capsule, and similar excret ion pattern of the metabolite. After both single and multiple dosing, piroxicam was absorbed more rapidly after CHF1194, an expected consequ ence of the complexation of piroxicam with beta-cyclodextrin. This may be of therapeutic interest as it might accelerate the onset of pain r elief. The pharmacokinetics of piroxicam was linear after the doses us ed here, suggesting that long term treatment with CHF1194 should not r equire any change in dosing regimen. Even after 14 days of repeated ad ministration of CHF1194, beta-cyclodextrin could not be detected in pl asma or urine, suggesting that in man the unchanged oligosaccharide wa s absorbed to a very small extent.