Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery--a pilot study.
The perioperative administration of selective cyclooxygenase-2 (COX-2)-inhibitors to avoid postoperative pain is an attractive option: they show favorable gastro-intestinal tolerability, lack inhibition of blood coagulation, and carry a low risk of asthmatic attacks. The purpose of this study was to determine the cerebrospinal fluid (CSF), plasma, and tissue pharmacokinetics of orally administered etoricoxib and to compare it with effect data, i.e., COX-2-inhibition in patients after hip surgery. The study was performed in a blinded, randomized, parallel group design. A total of 12 adult patients were included who received 120 mg etoricoxib (n = 8) or placebo (n = 4) on day 1 post-surgery. Samples from plasma, CSF, and tissue exudates were collected over a period of 24 h post-dosing and analyzed for etoricoxib and prostaglandin E(2) (PGE(2)) using liquid chromatography-tandem mass spectrometry and immuno-assay techniques. CSF area under the curve (AUC) [AUCs((O-24h))] for etoricoxib amounted to about 5% of the total AUC in plasma (range: 2-7%). Individual CSF lag times with respect to (50%) peak plasma concentration were </=2 h in all but one case (median: 1 h). PGE(2) production in tissue was significantly blocked by the COX-2 inhibitor starting with the appearance of etoricoxib in tissue and lasting for the whole observation period of 24 h (P < 0.01). In conclusion, etoricoxib reaches the CSF and site of surgery at effective concentrations and reduces PGE(2) production at the presumed site of action.
Renner
Bertold
B
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Krankenhausstr. 9, 91054 Erlangen, Germany. renner@pharmakologie.uni-erlangen.de
Zacher
Josef
J
Buvanendran
Asokumar
A
Walter
Gerrit
G
Strauss
Jochen
J
Brune
Kay
K
D000042:Absorption; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D019644:Arthroplasty, Replacement, Hip; D002853:Chromatography, Liquid; D052246:Cyclooxygenase 2 Inhibitors / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy; D010865:Pilot Projects; D011458:Prostaglandins E / Q000378:metabolism; D011725:Pyridines / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D013450:Sulfones / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
D052246:Cyclooxygenase 2 Inhibitors; D011458:Prostaglandins E; D011725:Pyridines; D013450:Sulfones; D000077613:Etoricoxib