| Oral bioavailability of the antiretroviral agent 9-(2-phosphonylmethoxyethyl)adenine (PMEA) from three formulations of the prodrug bis(pivaloyloxymethyl)-PMEA in fasted male cynomolgus monkeys. | |
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MedLine Citation:
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PMID: 7937523 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The bioavailability of PMEA from three oral formulations of the prodrug bis(POM)-PMEA has been evaluated in fasted male cynomolgus monkeys. The formulations examined included a hydroxypropyl-beta-cyclodextrin (HPBCD) complex, a PEG based cosolvent solution, and an aqeous suspension. Oral formulations containing 3H-bis(POM)-PMEA were compared to intravenous 3H-PMEA at 10.9 mg-eq/kg in a crossover study in four monkeys, with a 7 day washout period. No intact bis(POM)-PMEA or monoester were detected in plasma. Bioavailabilities of PMEA from the prodrug were 24.7 +/- 6.5%, 27.3 +/- 12.3% and 22.2 +/- 15.6% for the HPBCD complex, PEG solution and aqueous suspension, respectively. The oral bioavailability of PMEA from bis(POM)-PMEA was not limited by dissolution rate of the prodrug. Data for the PEG cosolvent solution and suspension indicate that the prodrug could potentially be formulated as a soft gelatin capsule or a tablet. |
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Authors:
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K C Cundy; J A Fishback; J P Shaw; M L Lee; K F Soike; G C Visor; W A Lee |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Pharmaceutical research Volume: 11 ISSN: 0724-8741 ISO Abbreviation: Pharm. Res. Publication Date: 1994 Jun |
Date Detail:
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Created Date: 1994-11-09 Completed Date: 1994-11-09 Revised Date: 2006-11-15 |
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: 839-43 Citation Subset: IM |
Affiliation:
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Gilead Sciences, Inc., Foster City, California 94404. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenine
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administration & dosage,
analogs & derivatives*,
pharmacokinetics Animals Antiviral Agents / administration & dosage, pharmacokinetics* Biological Availability Cyclodextrins Macaca fascicularis Male Phosphonic Acids* Prodrugs / administration & dosage, pharmacokinetics* Propylene Glycols Retroviridae / drug effects Suspensions beta-Cyclodextrins* |
| Chemical | |
Reg. No./Substance:
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0/Antiviral Agents; 0/Cyclodextrins; 0/Phosphonic Acids; 0/Prodrugs; 0/Propylene Glycols; 0/Suspensions; 0/beta-Cyclodextrins; 0/bis(pivaloyloxymethyl)-9-(2-phosphonylmethoxyethyl)adenine; 106941-25-7/adefovir; 73-24-5/Adenine; 94035-02-6/2-hydroxypropyl-beta-cyclodextrin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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