Transdermal Ketoprofen 

Clin J Sport Med. 2003 Jul;13(4):200-8.  
Efficacy of transdermal ketoprofen for delayed onset muscle soreness

OBJECTIVE: To determine the efficacy of transdermal ketoprofen in reducing delayed-onset muscle soreness (DOMS), limiting systemic absorption, and improving postexercise function following repetitive muscle contraction. DESIGN: Double-blind, placebo-controlled clinical trial. SETTING: OrthoMed, University of California at San Diego, La Jolla, CA, U.S.A. PARTICIPANTS: Thirty-two healthy males 18 to 35 years old. INTERVENTIONS: Subjects performed a leg extension and flexion exercise program designed to create DOMS in quadriceps muscles. Subjects were randomly assigned to receive any combination of transdermal ketoprofen or placebo cream, applied TID, to their right and left quadriceps. MAIN OUTCOME MEASURES: Subjective measure of DOMS in quadriceps muscles, serum ketoprofen levels, strength index scores (a measure of postexercise function), and adverse reactions were assessed at baseline, 24 hours, and 48 hours. RESULTS: Within-subjects analysis (n = 16) showed a significant reduction in DOMS scores in legs receiving transdermal ketoprofen compared with legs receiving placebo cream (P = 0.002 at 48 hours and 0.000 at 24 and 48 hours combined). Between-subjects analysis (n = 16) showed a marginally significant reduction in DOMS scores at 48 hours (P = 0.05 in right legs and 0.053 in left legs). Systemic absorption was minimal, with serum ketoprofen levels in the ng/mL range. No differences in strength index scores were observed. No adverse reactions were reported. CONCLUSIONS: Transdermal ketoprofen appears to be effective in reducing self-reported DOMS after repetitive muscle contraction, particularly after 48 hours. Systemic absorption of the drug was minimal. Treatment did not appear to have any effect on postexercise function, and there were no reported adverse reactions.

PMID: 12855921 [PubMed - indexed for MEDLINE]

Clin Ther. 1996 May-Jun;18(3):497-507.
Comparison of ketoprofen, piroxicam, and diclofenac gels in the treatment of acute soft-tissue injury in general practice. General Practice Study Group
Patel RK, Leswell PF.
Garrison Medical Centre, Woolwich, London, United Kingdom.

The efficacy, tolerability, and acceptability of topical applications of ketoprofen gel (2.5% w/w), piroxicam gel (0.5% w/w), and diclofenac gel (1% w/w), when administered three times daily for 5 days, in the treatment of acute (within 48 hours) soft-tissue injury, were compared in an open-label, randomized, multicenter, general practice study. Of 1575 patients recruited, 1048 received ketoprofen gel (525 used the gel with a dose-measuring device), 263 received piroxicam gel, and 264 received diclofenac gel. Ketoprofen gel was significantly superior to piroxicam gel in terms of global assessment of treatment response (improvement in 74% vs 65% of patients) and the severity of the injury (38% vs 26% "greatly improved") and in improvements in stiffness (71% vs 64%), restriction of mobility (34% vs 22%), and pain on pressure (81% vs 78%) and movement (83% vs 77%). Ketoprofen gel also compared favorably with diclofenac gel, with a larger proportion of patients assessing a great improvement in the injury (38% vs 30%). Patient acceptability of ketoprofen gel was significantly better than piroxicam gel. More patients noted a significant cooling effect with ketoprofen gel (71%) than with either piroxicam gel (49%) or diclofenac gel (60%). Ketoprofen gel also showed excellent tolerability. In conclusion, ketoprofen gel may offer benefits over established therapies for the treatment of acute soft-tissue injury.

PMID: 8829026 [PubMed - indexed for MEDLINE

Int J Pharm. 2008 Jun 5;357(1-2):295-304. Epub 2008 Feb 3.
Lipid nanoparticles for prolonged topical delivery: an in vitro and in vivo investigation.
Puglia C, Blasi P, Rizza L, Schoubben A, Bonina F, Rossi C, Ricci M.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Catania, viale A. Doria 6, 95125 Catania, Italy.

Dermal therapy is still a challenge due to the difficulties in controlling the active pharmaceutical ingredient (API) fate within the skin. Recently, lipid nanoparticles have shown a great potential as vehicle for topical administration of active substances, principally owing to the possible targeting effect and controlled release in different skin strata. Ketoprofen and naproxen loaded lipid nanoparticles were prepared, using hot high pressure homogenization and ultrasonication techniques, and characterized by means of photo correlation spectroscopy and differential scanning calorimetry. Nanoparticle behavior on human skin was assessed, in vitro, to determine drug percutaneous absorption (Franz cell method) and, in vivo, to establish the active localization (tape-stripping technique) and the controlled release abilities (UVB-induced erythema model). Results demonstrated that the particles were able to reduce drug penetration increasing, simultaneously, the permeation and the accumulation in the horny layer. A prolonged anti-inflammatory effect was observed in the case of drug loaded nanoparticles with respect to the drug solution. Direct as well as indirect evidences corroborate the early reports on the usefulness of lipid nanoparticles as carriers for topical administration, stimulating new and deeper investigations in the field.

PMID: 18343059 [PubMed - indexed for MEDLINE]

Int J Pharm. 2008 Aug 6;360(1-2):29-39. Epub 2008 Feb 6.
Preclinical characterisation of NSAIDs in ultradeformable carriers or conventional topical gels.
Cevc G, Mazgareanu S, Rother M.
IDEA AG, Frankfurter Ring 193a, D-80807 Munich, Germany.

We compared in vivo transport and biodistribution of ketoprofen applied on the skin in ultradeformable carriers (Diractin) or a conventional topical gel (Gabrilen) with oral drug (Oruvail); for reference we used in vitro study data. The drug from Gabrilen diffuses into body with low bioavailability (<10%) and limited regio-selectivity (AUC(deep muscle/plasma) approximately 45/0.8 (t=0-8h), reaching maximum concentration in subcutaneous tissues and plasma at similar time (t(max) approximately 3-4h). The apparent drug elimination half-life is then similar to oral ketoprofen (t1/2,a) approximately 2 h). In contrast, Diractin containing ultradeformable carriers (Transfersome vesicles) delivers the drug more efficiently (>50%) and more directly into peripheral muscles (AUC(deep muscle/plasma) approximately 447/0.7 (652/1.4) for t=0-8 (0-24)h; tmax approximately 1 h), arguably in non-diffusive fashion. Ketoprofen from Diractin moreover disappears from body periphery slower (t1/2,a) approximately 4-6 h), owing to sustained drug release from the carriers in target tissue. Final clearance always proceeds via plasma (tmax approximately 4 h). Epicutaneous application of ketoprofen in conventional gels or the carrier-based formulation thus leads to different local accumulations and clearances. Ketoprofen from Diractin achieves more desirable biodistribution and clearance, arguably due to spontaneous carrier-mediated drug transport across the skin, which ensures local and relatively long-lasting drug deposition into peripheral target tissues.

PMID: 18337027 [PubMed - in process]