Comparison of tissue concentrations after intramuscular and topical administration of ketoprofen.
OBJECTIVE
To assess whether topical ketoprofen, which has been reported to provide analgesic effects in clinical studies, reaches predictable tissue concentrations high enough to account for the reported analgesia. Intramuscular ketoprofen was used as positive control.


METHODS
Muscle and subcutaneous tissue concentrations were assessed by microdialysis. 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 tissue concentrations of 12 subjects that did not participate in the present study.


RESULTS
Most dialysate concentrations after topical dosing of ketoprofen (100 mg) were below the quantification limit of 0.47 ng/ml. Plasma concentrations 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 intramuscular injection (100 mg) were about 10 times higher than those after topical dosing. Tissue concentrations measured in the majority of the 12 subjects that did not participate in the present study were found within the range of two-thirds of the predicted concentrations.


CONCLUSIONS
Predictable and cyclooxygenase-inhibiting concentrations of ketoprofen were achieved in subcutaneous and muscle tissue after intramuscular but not after topical dosing. Thus, the tissue concentrations of ketoprofen after topical administration can hardly explain the reported clinical efficacy of topical ketoprofen.
Tegeder
I
I
Zentrum der Pharmakologie, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt am Main, Germany.
Lötsch
J
J
Kinzig-Schippers
M
M
Sörgel
F
F
Kelm
G R
GR
Meller
S T
ST
Geisslinger
G
G
D000287:Administration, Topical; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D015314:Dialysis Solutions / Q000378:metabolism; D006801:Humans; D007273:Injections, Intramuscular; D007660:Ketoprofen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis / Q000379:methods; D009132:Muscles / Q000378:metabolism; D010477:Perfusion; D011897:Random Allocation; D014018:Tissue Distribution / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015314:Dialysis Solutions; D007660:Ketoprofen