Intra-articular penetration of ketoprofen and analgesic effects after topical patch application in rats

Shinkai, Norihiro; Korenaga, Kazuko; Mizu, Hideo; Yamauchi, Hitoshi

doi:10.1016/j.jconrel.2008.07.012

Cited by 39 publications

(22 citation statements)

References 29 publications

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“…Ketoprofen penetration kinetics following application as a transdermal therapeutic system (with the target being intra-articular inflammation) has been measured in the skin as well as in the knee joint by MD. Sufficient drug concentrations for inhibition of prostaglandin E 2 production were found in the joint [118] .…”

Section: Clinical Studies Of Pharmacokinetics In the Skinmentioning

confidence: 98%

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

Holmgaard

Nielsen

Benfeldt

2010

Skin Pharmacol Physiol

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Microdialysis (MD) in the skin is a unique technique for in vivo sampling of topically as well as systemically administered drugs at the site of action, e.g. sampling the unbound tissue concentrations in the dermis and subcutaneous tissue. MD as a research method has undergone significant development, improvement and validation during the last decade and has proved to be a versatile, safe and valuable tool for pharmacokinetic and pharmacodynamic studies. This review gives an overview of the current state and future perspectives of dermal MD sampling. Methodological issues such as choice of instrumentation, calibration and experimental procedures are discussed along with the analytical considerations necessary for successful sampling. Clinical MD studies in the skin are reviewed with emphasis on pharmacokinetic studies of topically applied drugs with or without impairment of skin barrier function by skin disease or barrier perturbation. A comparison between MD and other tissue sampling techniques reveals the advantages and limitations of the method. Subsequently, an in-depth discussion of the application of MD for the evaluation of bioavailability and bioequivalence of topical formulations is concluded by the current regulatory point of view. The future perspective includes further expansion and validation of the use of MD in the experimental and clinical setting as well as in the optimization of the method for regulatory purposes, i.e. the commercialization of bioequivalent, generic drug products.

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Section: Clinical Studies Of Pharmacokinetics In the Skinmentioning

confidence: 98%

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

Holmgaard

Nielsen

Benfeldt

2010

Skin Pharmacol Physiol

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“…Therefore, it is necessary to develop enhancement techniques to assist the skin penetration of KET, and extensive research has been done to find both topical and transdermal KET formulations. 1,[4][5][6] To improve the delivery of KET through the skin, several techniques have been employed as follows: liposomes, 7) gels, 8,9) ointments, creams, 10) patches 11,12) incorporating various permeation enhancers, micro-needle treatment, 13) iontophoresis 14,15) and therapeutic frequency sonophoresis (1 MHz). 16,17) Recently, strategies using nanoparticles have been developed and investigated as nanomedicines.…”

mentioning

confidence: 99%

Pharmacokinetics and Antiinflammatory Effect of a Novel Gel System Containing Ketoprofen Solid Nanoparticles

Nagai

Iwamae

Tanimoto

et al. 2015

Biological & Pharmaceutical Bulletin

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We previously reported that dermal application using nanoparticles improves skin penetration. In this study, we prepared novel topical formulations containing ketoprofen (KET) solid nanoparticles (KET nano gel ointment) and investigated the antiinflammatory effect of the KET nanoparticle formulations on rheumatoid arthritis using adjuvant-induced arthritis (AA) rats. The KET nano gel ointment was prepared using a bead mill method and additives including methylcellulose and Carbopol 934; the mean particle size of the KET nanoparticles was 83 nm. In the in vitro skin penetration experiment, the penetration rate (J c ) and penetration coefficient through the skin (K p ) values of the KET nano gel ointment were significantly higher than those of gel ointment containing KET microparticles (KET micro gel ointment; mean particle size 7.7 µm). On the other hand, in the in vivo percutaneous absorption experiment, the apparent absorption rate constant (k a ) and the areas under the KET concentration-time curve values in the skin of rats receiving the KET nano gel ointment were significantly higher than those of rats receiving the KET micro gel ointment, and the amounts of KET in the skin tissues of rats receiving the KET nano gel ointment were also significantly higher than those of rats receiving the KET micro gel ointment. In addition, the application of the KET nano gel ointment attenuated the enhancement of paw edema of the hind feet of AA rats more than the application of the KET micro gel ointment. Our findings suggest that a topical drug delivery system using nanoparticles could lead to expansion in the therapeutic use of KET.Key words nanoparticle; ketoprofen; gel ointment; drug delivery; adjuvant-induced arthritis Ketoprofen (KET) is a reversible inhibitor of cyclooxygenases 1 and 2 whose action leads to a reduction in the formation of prostaglandin precursors. 1) Thus, KET acts as an antiinflammatory agent, and is used in the treatment of rheumatoid arthritis (RA) and osteoarthritis. However, its usefulness is limited due to its low water solubility and the fact that oral administration of KET tends to cause gastrointestinal lesions in 10-30% of patients. These gastrointestinal lesions lead to an interruption of drug therapy in about 5-15% patients. 2,3)Topical and transdermal delivery routes of drug administration reduce the incidence of gastrointestinal lesions and improve patient compliance. Furthermore, the transdermal route of application avoids hepatic first pass metabolism, meaning that therapeutic serum drug concentrations can be applied with a reduced risk of nephrotoxicity and drug-drug interactions.2) However, the transdermal route of application is limited by the barrier properties of the skin. Therefore, it is necessary to develop enhancement techniques to assist the skin penetration of KET, and extensive research has been done to find both topical and transdermal KET formulations.

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“…Shinkai et al [95] using the croton oil to establish the rat skin inflammation model, after the MD probe was implanted in the subcutaneous, then given the felbinac patch, the MD sample drug concentration was measured, wherein the PGE-2 levels were measured, the results showed that croton oil significantly increased the subcutaneous PGE-2 levels, while providing 0.5% or 3.5% felbinac patch after 2~5 h, the PGE-2 levels were significantly decreased. In Shinkai et al [96] another study had proven that the transdermal ketoprofen significantly reduced the PGE-2 skin content and the joint fluid. Brazis et al [97] studied the impact cyclosporin A on the Beagle dogs skin histamine and PGE-2 levels, the results showed that histamine levels were significantly decreased after treatment 15~30 days, but the PGE-2 levels did not change significantly, indicating that cyclosporine inhibiting the release of anti-inflammatory effects of histamine.…”

Section: The Pharmacodynamics and Mechanism Studymentioning

confidence: 97%

Crosstalk the Microdialysis in Scientific Research: from Principle to its Applications

Lee¹,

Di²

2013

Pharm Anal Acta

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Intra-articular penetration of ketoprofen and analgesic effects after topical patch application in rats

Cited by 39 publications

References 29 publications

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

Microdialysis Sampling for Investigations of Bioavailability and Bioequivalence of Topically Administered Drugs: Current State and Future Perspectives

Pharmacokinetics and Antiinflammatory Effect of a Novel Gel System Containing Ketoprofen Solid Nanoparticles

Crosstalk the Microdialysis in Scientific Research: from Principle to its Applications

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