Relative bioavailability of ketoprofen 20% in a poloxamer-lecithin organogel.
OBJECTIVE
The bioavailability of a single, topically applied, 200-mg dose of ketoprofen (delivered in a ketoprofen 20% gel) relative to a single 50-mg oral dose in healthy volunteers was studied.


METHODS
This was an open-label crossover study. The subjects were randomized to receive an oral 50-mg ketoprofen capsule or a single topical dose of ketoprofen 20% in a poloxamer-lecithin organogel (PLO). Treatment was followed by a one-week washout period. Blood samples were collected at intervals up to 10 hours after administration, and plasma ketoprofen concentrations were determined by high-performance liquid chromatography with ultraviolet or mass spectrometry detection. Noncompartmental pharmacokinetic values were obtained after each dose, and relative bioavailability was calculated.


RESULTS
Eight healthy volunteers enrolled in and completed the study. Topical absorption of ketoprofen was highly variable among the subjects over the 10-hour sampling period. The median oral maximum plasma concentration (Cmax) exceeded the topical Cmax by nearly 200-fold (4.15 versus 0.021 microg/mL) (p = 0.001). The median relative bioavailability of topical ketoprofen was 0.48%, with individual subjects' values ranging from 0.18% to 2.1%.


CONCLUSIONS
The relative bioavailability of ketoprofen was low and highly variable when the drug was administered as a single dose in a PLO-based ketoprofen 20% gel.
Dowling
Thomas C
TC
Pharmacokinetics and Biopharmaceutics Laboratory, Department of Pharmacy and Therapeutics, School of Pharmacy, University of Maryland, Baltimore 21201, USA.
Arjomand
Mahiyar
M
Lin
Emil T
ET
Allen
Loyd V
LV
McPherson
Mary Lynn
ML
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005079:Excipients; D005782:Gels; D006801:Humans; D007660:Ketoprofen / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D010713:Phosphatidylcholines; D020442:Poloxamer; D012869:Skin Absorption
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D005782:Gels; D010713:Phosphatidylcholines; D020442:Poloxamer; D007660:Ketoprofen