piroxicam-beta-cyclodextrin and betadex

CHF1194 is an inclusion complex of beta-cyclodextrin with the nonsteroidal 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 of the drug is increased whilst its other pharmacokinetic characteristics remain unchanged. The aim of the present study in 12 healthy subjects was to compare the oral bioavailability of 20 mg piroxicam in a CHF1194 tablet and a plain piroxicam capsule after a single dose and after two weeks of once daily administration, and also to assess the plasma levels and urinary excretion of beta-cyclodextrin after CHF1194 administration. The two treatments were administered in cross-over fashion, separated by a wash-out period of three weeks. Piroxicam, 5'-hydroxypiroxicam and beta-cyclodextrin were monitored in plasma and urine for 120 h after the first and last doses. Clinical tolerance was excellent and no adverse event occurred during either phase of the study. The extent of absorption of piroxicam from the CHF1194 tablet after the single dose was equivalent to that after the plain piroxicam capsule, within confidence limits of less than 80-125%. After repeated dosing, CHF1194 yielded the same steady-state systemic concentrations of piroxicam and 5'-hydroxypiroxicam as the reference capsule, and similar excretion pattern of the metabolite. After both single and multiple dosing, piroxicam was absorbed more rapidly after CHF1194, an expected consequence of the complexation of piroxicam with beta-cyclodextrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Biological Availability; Cross-Over Studies; Cyclodextrins; Drug Combinations; Female; Humans; Male; Piroxicam

Piroxicam beta-cyclodextrin is a novel inclusion complex in which the piroxicam molecule has higher wettability and faster dissolution characteristics than plain piroxicam. Pharmacokinetic studies comparing piroxicam beta-cyclodextrin with plain piroxicam have been carried out in both patients and healthy subjects. The absorption rate of piroxicam from the complex, determined using tmax, absorption rate constant (Ka) and plasma concentrations at 15 min and 30 min post-dose, is considerably faster than that for plain piroxicam. This difference, that can be demonstrated with both tablet and sachet formulations, is still present during repeated dose administration and when the drugs are administered after food. After absorption from piroxicam beta-cyclodextrin formulations, the kinetic disposition of piroxicam and bioavailability parameters are identical to those for plain piroxicam. The more rapid rise in piroxicam plasma concentrations and the reduced contact time of piroxicam in the upper gastrointestinal-tract may be reasons for the reduced incidence of gastrointestinal complaints and gastrointestinal bleeding and the rapid attainment of pain relief with piroxicam beta-cyclodextrin. The most rapid relief of pain will be achieved using piroxicam beta-cyclodextrin sachets administered in the fasting state, since piroxicam is immediately bioavailable in this formulation and the onset of action is similar to that for injectable piroxicam.

Topics: Absorption; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; beta-Cyclodextrins; Cross-Over Studies; Cyclodextrins; Digestive System; Drug Combinations; Female; Follow-Up Studies; Food; Humans; Male; Molecular Structure; Piroxicam