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Diclofenac concentrations in defined tissue layers after topical administration
Author(s) -
Müller Markus,
Mascher Hermann,
Kikuta Christian,
Schäfer Sabine,
Brunner Martin,
Dorner Guido,
Eichler Hans Georg
Publication year - 1997
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(97)90032-1
Subject(s) - microdialysis , diclofenac , transdermal , in vivo , area under the curve , pharmacokinetics , medicine , penetration (warfare) , pharmacology , chemistry , biomedical engineering , anesthesia , biology , microbiology and biotechnology , operations research , engineering
To date it is unclear whether therapeutic concentrations are attained in target tissues after topical administration of nonsteroidal anti‐inflammatory drugs. Therefore this study in healthy volunteers was undertaken to measure diclofenac concentrations attained in defined tissue layers directly underlying the site of topical diclofenac application by in vivo microdialysis. Methods In each experiment two microdialysis probes were inserted, one into a superficial (3.9 ± 0.3 mm) and one into a deep (9.3 ± 0.5 mm) tissue layer, in 20 healthy volunteers and calibrated in vivo. The distance between the surface of the skin and the tips of the microdialysis probes was measured by 7.5 MHz ultrasound. Diclofenac was administered topically as a single dose of approximately 300 mg/100 cm 2 . Concentration versus time profiles in tissue layers were monitored for 5 hours. Results Concentration versus time profiles were obtained in 11 of 20 experiments. However, there was no correlation between area under the concentration‐time curve (AUC) in a defined layer and the depth of probe insertion. In those experiments where concentration versus time profiles were obtained for both probes mean AUC was 532 ± 197 μg · min · ml −1 for superficial layers, and 438 ± 249 μg · min · ml −1 for deep layers. Conclusion We conclude that transdermal penetration of diclofenac, at least after single doses, is not predictable and may strongly be influenced by individual skin properties. Clinical Pharmacology & Therapeutics (1997) 62 , 293–299; doi: