Oral bioavailability of CHF1194, an inclusion complex of piroxicam and β-cyclodextrin, in healthy subjects under single dose and steady-state conditions
✍ Scribed by X. Deroubaix; A. Stockis; A. M. Allemon; E. Lebacq; D. Acerbi; P. Ventura
- Publisher
- Springer
- Year
- 1995
- Tongue
- English
- Weight
- 672 KB
- Volume
- 47
- Category
- Article
- ISSN
- 0031-6970
No coin nor oath required. For personal study only.
✦ Synopsis
CHFl194 is an inclusion complex of fl-cyclodextrin with the nonsteroidal anti-inflammatory drug piroxicam. In man, fl-cyclodextrin acts as a carrier of piroxicam. As the inclusion complex of piroxicam-flcyclodextrin 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 CHFl194 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 fl-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 flcyclodextrin 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 CHFl194 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, CHFl194 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 CHFl194, an expected consequence of the complexation of piroxicam with fl-cyclodextrin. This may be of therapeutic interest as it might accelerate the onset of pain relief.
The pharmacokinetics of piroxicam was linear after the doses used here, suggesting that long term treatment with CHFl194 should not require any change in dosing X. Deroubaix (~) • A. Stockis • A.