Supermolecular inclusion of piroxicam with beta-cyclodextrin: pharmacokinetic properties in man.
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.
Woodcock
B G
BG
Chemical and Biopharmaceutical Research Department, Chiesi Farmaceutici S.p.A., Parma, Italy.
Acerbi
D
D
Merz
P G
PG
Rietbrock
S
S
Rietbrock
N
N
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004064:Digestive System / Q000187:drug effects; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D005502:Food; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010894:Piroxicam / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D047392:beta-Cyclodextrins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D004338:Drug Combinations; D047392:beta-Cyclodextrins; D010894:Piroxicam; C061072:piroxicam-beta-cyclodextrin; C031215:betadex