Comparison of tissue concentrations after intramuscular and topical administration of ketoprofen

Purpose. To assess whether topical ketoprofen, which has been reported to p rovide analgesic effects in clinical studies, reaches predictable tissue co ncentrations high enough to account for the reported analgesia. Intramuscul ar ketoprofen was used as positive control. Methods, Muscle and subcutaneous tissue concentrations were assessed by mic rodialysis. Plasma and tissue concentrations after intramuscular injection were described using a three-compartment population pharmacokinetic model. The prediction performance of the model was assessed by superimposing tissu e concentrations of 12 subjects that did not participate in the present stu dy. Results, Most dialysate concentrations after topical dosing of ketoprofen ( 100 mg) were below the quantification limit of 0.47 ng/ml. Plasma concentra tions increased slowly and reached an apparent plateau of 7-40 ng/ml at 10- 12h. No decline was observed up to 16 h. Tissue concentrations after intram uscular injection (100 mg) were about 10 times higher than those after topi cal dosing. Tissue concentrations measured in the majority of the 12 subjec ts that did not participate in the present study were found within the rang e of two-thirds of the predicted concentrations. Conclusion. Predictable and cyclooxygenase-inhibiting concentrations of ket oprofen were achieved in subcutaneous and muscle tissue after intramuscular but not after topical dosing. Thus. the tissue concentrations of ketoprofe n after topical administration can hardly explain the reported clinical eff icacy of topical ketoprofen.