Stereoselective pharmacokinetics of ketorolac in calves after a single intravenous and oral dose.
The purpose of this study was to establish the stereospecific pharmacokinetics of ketorolac (KT) in calves following a single 2 mg/kg intravenous (i.v.) and a single 8 mg/kg oral dose. Plasma concentrations were determined using a stereoselective HPLC assay. Pharmacokinetic parameters for both the stereoisomers were estimated by model-independent methods. Following an i.v. dose, the plasma concentration profiles of the stereoisomers were similar with half-lives of 5.9 +/- 5.1 h for R-KT and 6.0 +/- 4.9 h for S-KT. Clearance values for R- and S-KT after an i.v. dose were 0.0470 +/- 0.0370 and 0.0480 +/- 0.0370 L/h/kg respectively. After an oral dose, the terminal half-lives were longer than following i.v. administration with values of 14.77 +/- 3.08 and 14.55 +/- 2.95 h for R-KT and S-KT respectively. The average oral bioavailability was 86.5 +/- 20.6% for R-KT and 86.7 +/- 20.3% for S-KT. The results indicate that the stereoisomers of KT have similar pharmacokinetic profiles in calves. Although, unlike humans, bioinversion between KT stereoisomers appears minimal in calves, studies with individual isomers are needed before any firm conclusions can be drawn about this lack of KT bioinversion.
Nagilla
R
R
GlaxoSmithKline, King of Prussia, PA 19406, USA. rakesh.2.nagilla@gsk.com
Deshmukh
D D
DD
Duran
S H
SH
Ravis
W R
WR
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002417:Cattle / Q000378:metabolism*; D018592:Cross-Over Studies; D007275:Injections, Intravenous / Q000662:veterinary; D007536:Isomerism; D020910:Ketorolac / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male