Clinical pharmacokinetics of parenteral dexketoprofen trometamol in healthy subjects

Dexketoprofen trometamol, a highly water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug used for pain relief. Two studies were conducted to determine the pharmacokineties of the drug in healthy subjects following single intravenous (i.v.) and intramuscular (i.m.) doses of dexketoprofen. In the first study, 6 male and 6 female volunteers received 50 mg dexketoprofen (74 mg dexketoprofen trometamol) by i.v. bolus. In the second one, another 6 male and 6 female subjects received 25 mg and 50 mg of dexketoprofen by the i.m. route. Dexketoprofen plasma concentrations were determined by reverse-phase high-performance liquid chromatography (HPLC). No serious adverse events were observed and all volunteers completed the study. The main pharmacokinetic parameters were determined by a noncompartmental approach. Following the i.v. bolus, mean (+/- SEM) area under the curve AUC(0-x) and clearance (CL) were 9005 +/- 422 ng(.)h/ml and 0.089 +/- 0.004 l/h/kg. Volumes of distribution V-i and V-ss averaged 0.060 +/- 0.006 l/kg and 0.104 +/- 0.003 l/kg. Mean elimination half-life (t(1/2e)) and MRT were 1.05 +/- 0.04 h and 1.18 +/- 0.05 h. Following single i.m. 25 mg and 50 mg dexketoprofen, a rapid absorption was observed, with t(max) values ranging from 0.17 h to 0.75 h. The corresponding C-max averaged 1851 +/- 182 ng/ml and 3813 +/- 169 ng/ml, and mean AUC(0-x) were 3033 +/- 193 ng(.)h/ml and 5878 +/- 228 ng(.)h/ml, respectively. No significant differences by gender were obtained following both parenteral routes. A dose proportionality in C-max and AUC(0-x) was observed. Dexketoprofen pharmacokinetics following i.v. and i.m. routes, together with the availability of a single 2 ml formulation, allows for a potential advantageous rapid switch to the oral formulation when clinically possible. (c) 2006 Prous Science. All rights reserved.