Pharmacokinetics of ketorolac tromethamine in rabbit plasma

Objective:To study the pharmacokinetics of ketorolac tromethamine after i.v.and transdermal gel ad- ministration in rabbits.Method:An HPLC method was established using gliquidone as internal standard.Plasma samples were deproteinized with acetonitrile,the supernant was added 1μL of acetic acid(0.1%).Kromasil C_(18) (200 mm×4.6 mm,5μm)was used at column temperature 30℃.The mobile phase consisted of methanol-water -triethylamine-acetic acid(80:19:9:0.02:0.08)at the flow of 1.0 mL·min~(-1).The UV detection wavelength was set at 313 nm.Results:The calibration curve was shown to be linear over the range from 0.1 to 100μg·mL~(-1) (r=0.9981).The mean recovery was 78.6%-98.6%.The RSDs of within-day and between-day were all less than 14.7%.The main pharmacokinetic parameters were estimated as follows:injection:α=(14.2±6.6)h~(-1),β= (1.3±0.3)h~(-1),T_(1/2α)=(0.06±0.02)h,T_(1/2β)=(0.6±0.2)h,AUC_(0-t)=(18.1±0.5)μg·h·mL~(-1),AUC_(0-∞) =(20.5±1.6)μg·h·mL~(-1);transderrnal gel:α=(0.7±0.2)h~(-1),β=(0.3±0.1)h~(-1),T_(1/2α)=(1.3±0.6) h,T_(1/2β)=(4.4±1.7)h,AUC_(0-t)=(4.9±1.9)μg·h·mL~(-1),AUC_(0-∞)=(6.3±2.6)μg·h·mL~(-1).Conclu- sion:The validated HPLC method is specific,simple,sensitive and suitable for the measurement of plasma ketorolac tromethamine concentration.The pharmacokinetie characteristics are fitted with the two-compartment model.