Passive versus electrotransport-facilitated transdermal absorption of ketorolac.
OBJECTIVE
To investigate the bioavailability (extent and rate of absorption) of ketorolac from two cutaneous absorption sources, active electrotransport and passive transdermal, and to examine the enantiomeric selectivity of bioavailability for each source.


METHODS
Based on a crossover study in 12 healthy volunteers, the extent and rate of absorption of ketorolac, delivered by a patch, were found by estimating the input rate function of the drug. For that purpose, deconvolution was used in two steps. First, intravenous data were analyzed to estimate the ketorolac disposition function, and second, postpatch data were deconvolved to estimate the unknown patch input profile given the disposition function estimated in the first step. Because the input rate function curves to be estimated for the patches may be of arbitrary shape, a spline was used to model the patch input function, whereas intravenous data were modeled with use of a sum of exponentials. Differences in the extent of absorption (F) for the four treatment-enantiomer combinations were further examined with a mixed-effect regression model, based on the sets of four individual estimates of bioavailability.


RESULTS
On average, the F value for the active electrotransport treatment, which exhibited the faster absorption rate, was four times greater than the F for the passive transdermal treatment. Further, during the passive treatment, R-ketorolac yielded an average F that is 42% greater than that for S-ketorolac and also exhibited a smaller absorption lag-time. During the active treatment, there was no important enantiomeric difference in either extent or rate of absorption.
Park
K
K
Department of Biopharmaceutical Sciences, University of California, San Francisco, USA.
Verotta
D
D
Gupta
S K
SK
Sheiner
L B
LB
D000279:Administration, Cutaneous; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D001692:Biological Transport; D001693:Biological Transport, Active; D006801:Humans; D020910:Ketorolac; D016014:Linear Models; D008297:Male; D012016:Reference Values; D012867:Skin / Q000378:metabolism*; D013237:Stereoisomerism; D013997:Time Factors; D014046:Tolmetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014046:Tolmetin; D020910:Ketorolac