| The physicochemical properties, plasma enzymatic hydrolysis, and nasal absorption of acyclovir and its 2'-ester prodrugs. | |
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MedLine Citation:
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PMID: 8165182 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A series of 2'-(O-acyl) derivatives of 9-(2-hydroxyethoxymethyl)guanine (acyclovir) was synthesized by acid anhydride esterification. Aqueous solubilities in isotonic phosphate buffer (pH 7.4), partition coefficients in 1-octanol/phosphate buffer, and hydrolysis kinetics in rat plasma were determined. The ester prodrugs showed consistent increases in lipophilicity with corresponding decreases in aqueous solubility as a function of side-chain length. The bioconversion kinetics of the prodrugs appear to depend on both the apolar and the steric nature of the acyl substituents. When perfused through the rat nasal cavity using the in situ perfusion technique, acyclovir showed no measurable loss from the perfusate. Nasal uptake of acyclovir prodrugs, on the other hand, were moderately improved. Furthermore, the extent of nasal absorption appears to depend on the lipophilicity of the prodrugs in the descending order hexanoate > valerate > pivalate > butyrate. Simultaneous prodrug cleavage by nasal carboxylesterase was also noted in the case of hexanoate. |
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Authors:
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Z Shao; G B Park; R Krishnamoorthy; A K Mitra |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Pharmaceutical research Volume: 11 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 1994 Feb |
Date Detail:
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Created Date: 1994-05-24 Completed Date: 1994-05-24 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 237-42 Citation Subset: IM |
Affiliation:
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Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907-1336. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Absorption Acyclovir / administration & dosage, blood, metabolism, pharmacokinetics* Administration, Intranasal Animals Buffers Carboxylesterase Carboxylic Ester Hydrolases / metabolism Esterification Esters Hydrogen-Ion Concentration Hydrolysis Male Nasal Mucosa / metabolism* Prodrugs / administration & dosage, chemistry, metabolism, pharmacokinetics* Rats Rats, Sprague-Dawley Solubility |
| Grant Support | |
ID/Acronym/Agency:
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NS 25284/NS/NINDS NIH HHS; RR 05586/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Buffers; 0/Esters; 0/Prodrugs; 59277-89-3/Acyclovir; EC 3.1.1.-/Carboxylic Ester Hydrolases; EC 3.1.1.1/Carboxylesterase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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