Stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug.
This review is written to evaluate the stereoselectivity in cutaneous hydrolysis and transdermal transport of propranolol prodrug. This discussion will be useful in the development of knowledge about stereoselective cutaneous hydrolysis and its influence on stereoselective transdermal transport of many other chiral prodrugs and drugs. Propranolol prodrugs undergo stereoselective hydrolysis in hairless mouse skin homogenate and in excised skin samples during permeation; the stereoselectivity is markedly biased towards hydrolysis of the (R) isomer. Unlike the liver, the esterase activity of the skin is high in its cytosolic fraction. Most of the lipophilic propranolol prodrugs cause stereoselective permeation across hairless mouse skin. A mechanism of stereoselective permeation of propranolol prodrug across the skin has been proposed, which indicates that the stereoselectivity in permeation is resulted from the stereoselective hydrolysis of lipophilic prodrug during permeation.
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
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Ahmed
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Imai
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Otagiri
D000818:Animals; D003600:Cytosol / Q000378:metabolism; D006868:Hydrolysis; D051379:Mice; D008812:Mice, Hairless; D008861:Microsomes / Q000378:metabolism; D011355:Prodrugs / Q000493:pharmacokinetics*; D011433:Propranolol / Q000493:pharmacokinetics*; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013237:Stereoisomerism
D011355:Prodrugs; D011433:Propranolol