Piroxicam concentrations in plasma and synovial fluid after a single dose of piroxicam-beta-cyclodextrin.
OBJECTIVE
The efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in rheumatic diseases depends on their concentrations within the joint. We determined piroxicam concentrations in plasma and synovial fluid (SF) after a single oral dose of 20 mg in the form of one tablet of piroxicam-beta-cyclodextrin.


METHODS
45 patients, aged 21 to 84 years, presenting with an effusion of the knee, related to degenerative or inflammatory joint disease, were included in this study after having given their written consent. One blood and one SF sample were drawn concomitantly in each patient from 0.5 to 48 h after NSAID administration. Piroxicam assays were performed by high performance liquid chromatography. Pharmacokinetic parameters were obtained from the mean plasma and synovial concentrations measured at various sampling times.


RESULTS
The peak concentration was higher in plasma (2.51+/-0.25 microg/ml) than in SF (1.31+/-0.76 microg/ml), but the elimination half-life was much longer in SF (90.7 h) than in plasma (32.5 h). The SF/plasma area under the concentration-time curve ratio (evaluating the quantity of NSAID transferred from the blood to the joint) was equal to 0.39.


CONCLUSIONS
Piroxicam contained in piroxicam-beta-cyclodextrin diffused well into the SF where its pharmacokinetic profile corresponded to that of a long half-life NSAID.
Bannwart
B
B
Rheumatology Department of Groupe Hospitalier Pellegrin, Bordeaux, France.
Bertin
P
P
Péhourcq
F
F
Schaeverbeke
T
T
Gillet
P
P
Lefrançois
G
G
Trèves
R
R
Dehais
J
J
Netter
P
P
Gaucher
A
A
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D003505:Cyclodextrins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D006801:Humans; D007592:Joint Diseases / Q000188:drug therapy; D007719:Knee Joint / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010894:Piroxicam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013582:Synovial Fluid / Q000737:chemistry; D047392:beta-Cyclodextrins
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003505:Cyclodextrins; D004338:Drug Combinations; D047392:beta-Cyclodextrins; D010894:Piroxicam; C061072:piroxicam-beta-cyclodextrin