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Critical Reviews™ in Therapeutic Drug Carrier Systems
Factor de Impacto: 2.9 Factor de Impacto de 5 años: 3.72 SJR: 0.736 SNIP: 0.551 CiteScore™: 2.43

ISSN Imprimir: 0743-4863
ISSN En Línea: 2162-660X

Volumes:
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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v17.i2.10
28 pages

Oral Delivery of HIV-Protease Inhibitors

Lilian Y. Li
College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065
Barbra H. Stewart
Parke-Davis/Warner-Lambert, Dept. of Pharmacokinetics, Dynamics, and Metabolism, 2800 Plymouth Rd., Ann Arbor, Michigan 48106-1047
David Fleisher
College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109-1065

SINOPSIS

Strategies for optimizing the oral delivery of HIV-protease inhibitors draw from drug discovery efforts in molecular design, drug development tools in dosage formulation, and dosage regimen considerations in clinical medicine. This review outlines the evolution of these strategies for drugs that have been approved for human use, drug candidates still in development, and molecules that are no longer in development but from which valuable delivery information was obtained. Molecular design for obtaining desirable pharmacokinetics following oral administration primarily involved maximizing aqueous solubility and minimizing first-pass metabolism. Optimization of molecular design for oral drug delivery purposes is tempered by additional considerations for drug potency, toxicity, potential for interactions, and development of viral resistance. Strategies for improving oral bioavailability dirough dosage formulation use information from the effects of coadministered meals on drug plasma levels. Patient adherence to dosage regimens remains a major issue in assuring effective oral drug treatment and in preventing the development of resistance. Progress has been made in clinical studies where improved oral bioavailability and reductions in drug plasma level variability have been achieved with appropriate dosage regimen adjustment.


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