Transdermal drug transport and metabolism. II. The role of competing kinetic events.
The steady-state flux and skin tissue distribution of a topically applied diester of salicylic acid was measured in vitro in the presence and absence of an esterase inhibitor. When compared with data obtained previously under in vivo conditions, the results presented here provide insight into the role of competing diffusional and hydrolytic events in the delivery and distribution of topically applied drugs. Furthermore, these results, when combined with a theoretical analysis of topical drug delivery and metabolism, suggest that the differences in delivery and drug distribution seen under in vitro conditions are related to both altered drug removal and altered hydrolysis rates.
Potts
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RO
Pfizer Central Research, Groton, Connecticut 06340.
McNeill
S C
SC
Desbonnet
C R
CR
Wakshull
E
E
D000279:Administration, Cutaneous; D001692:Biological Transport; D004950:Esterases / Q000037:antagonists & inhibitors; D006801:Humans; D006868:Hydrolysis; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000494:pharmacology; D012459:Salicylates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012867:Skin / Q000201:enzymology; D012869:Skin Absorption
D012459:Salicylates; D007531:Isoflurophate; D004950:Esterases