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Titolo:
Therapeutic drug monitoring of HIV protease inhibitors using high-performance liquid chromatography with ultraviolet or photodiode array detection
Autore:
Leibenguth, P; Le Guellec, C; Besnier, JM; Bastides, F; Mace, M; Gaudet, ML; Autret-Leca, E; Paintaud, G;
Indirizzi:
Tours Univ Hosp, Dept Pharmacol, F-37044 Tours, France Tours Univ Hosp Tours France F-37044 pt Pharmacol, F-37044 Tours, France Tours Univ Hosp, Dept Internal Med & Infect Dis, F-37044 Tours, France Tours Univ Hosp Tours France F-37044 & Infect Dis, F-37044 Tours, France
Titolo Testata:
THERAPEUTIC DRUG MONITORING
fascicolo: 6, volume: 23, anno: 2001,
pagine: 679 - 688
SICI:
0163-4356(200112)23:6<679:TDMOHP>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN PLASMA; COMBINATION THERAPY; P-GLYCOPROTEIN; ANTIRETROVIRAL AGENTS; SAQUINAVIR; INDINAVIR; RITONAVIR; PHARMACOKINETICS; INFECTION;
Keywords:
HIV protease inhibitor; drug monitoring; high-pressure liquid chromatography;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Le Guellec, C Tours Univ Hosp, Dept Pharmacol, 2 Bd Tonnelle, F-37044 Tours, France Tours Univ Hosp 2 Bd Tonnelle Tours France F-37044 , France
Citazione:
P. Leibenguth et al., "Therapeutic drug monitoring of HIV protease inhibitors using high-performance liquid chromatography with ultraviolet or photodiode array detection", THER DRUG M, 23(6), 2001, pp. 679-688

Abstract

Published data suggest that therapeutic drug monitoring of human immunodeficiency virus protease inhibitors would improve the management of antiretroviral therapy. The authors have developed a high-pressure liquid chromatographic assay allowing simultaneous determination of six protease inhibitors (ritonavir, saquinavir, indinavir, nelfinavir, amprenavir, and lopinavir), using carbamazepine as internal standard. Detection was based on a dual wavelength ultraviolet spectrophotometer and can be improved by the use of a photodiode array detector. Monitoring was performed 1 month after initiationof therapy or in instances of therapeutic failure, side effects, suspicionof noncompliance, drug interactions, or malabsorption. Trough concentrations were 0.15 to 13.6 mg/L for ritonavir, 0.06 to 9.7 mg/L for indinavir, 0.03 to 5.5 mg/L for saquinavir, and 0.15 to 4.15 mg/L for nelfinavir. Concentrations below the limit of quantification were observed in 63/438 (14%) ofthe patients. Target concentrations are not well established, and reportedin vitro inhibitory concentrations may be of limited value. The authors therefore chose to compare observed concentrations with mean plasma concentrations reported in clinical trials. Observed saquinavir and indinavir concentrations were often below or close to these target concentrations, particularly when used as a single protease inhibitor. Concentration-controlled studies should now be used to select proper target concentrations for each protease inhibitor, either prescribed alone or in combination.

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Documento generato il 04/04/20 alle ore 11:39:32