A comparative study of the transdermal penetration of a series of nonsteroidal antiinflammatory drugs.
The transdermal absorption of a series of nonsteroidal antiinflammatory drugs (NSAIDs): indomethacin, ketoprofen, diclofenac, piroxicam, tenoxicam, ketorolac, and aceclofenac) was studied in vitro with human skin. The purpose of the study was to determine the permeation parameters (permeability rate constant, Kp; lag time, TL, and flux, J) as measures of the intrinsic transdermal permeabilities of these drugs to predict their potential for formulation in a transdermal therapeutic system (TTS). A linear correlation was established between the intrinsic log Kp values and the intrinsic partition coefficients (r = 0.863, p = 0.012, n = 7). Diclofenac had the highest value of in vitro transdermal penetration at approximately 0% ionization (Kp = 3.5 cm/h) and ketoprofen had the highest flux (J = 16 micrograms/h.cm2) of the NSAIDs assayed. Ketorolac would provide the plasma concentrations at steady state that would be nearest to the therapeutic concentration (Cr/Css = 26). Also, considering the whole permeation profile in vitro, ketorolac would be the most suitable candidate of the series studied to be formulated as a TTS.
Cordero
J A
JA
Pharmacokinetics and Biopharmaceutics Laboratory, School of Pharmacy, University of Barcelona, Núcleo Universitario Pedralbes, Spain.
Alarcon
L
L
Escribano
E
E
Obach
R
R
Domenech
J
J
D000279:Administration, Cutaneous; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D012869:Skin Absorption
D000894:Anti-Inflammatory Agents, Non-Steroidal