Therapeutic drug monitoring of HIV protease inhibitors using high-performance liquid chromatography with ultraviolet or photodiode array detection

Citation
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
Citations number
46
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
THERAPEUTIC DRUG MONITORING
ISSN journal
01634356 → ACNP
Volume
23
Issue
6
Year of publication
2001
Pages
679 - 688
Database
ISI
SICI code
0163-4356(200112)23:6<679:TDMOHP>2.0.ZU;2-R
Abstract
Published data suggest that therapeutic drug monitoring of human immunodefi ciency virus protease inhibitors would improve the management of antiretrov iral therapy. The authors have developed a high-pressure liquid chromatogra phic assay allowing simultaneous determination of six protease inhibitors ( ritonavir, saquinavir, indinavir, nelfinavir, amprenavir, and lopinavir), u sing carbamazepine as internal standard. Detection was based on a dual wave length ultraviolet spectrophotometer and can be improved by the use of a ph otodiode array detector. Monitoring was performed 1 month after initiation of therapy or in instances of therapeutic failure, side effects, suspicion of noncompliance, drug interactions, or malabsorption. Trough concentration s were 0.15 to 13.6 mg/L for ritonavir, 0.06 to 9.7 mg/L for indinavir, 0.0 3 to 5.5 mg/L for saquinavir, and 0.15 to 4.15 mg/L for nelfinavir. Concent rations below the limit of quantification were observed in 63/438 (14%) of the patients. Target concentrations are not well established, and reported in vitro inhibitory concentrations may be of limited value. The authors the refore chose to compare observed concentrations with mean plasma concentrat ions reported in clinical trials. Observed saquinavir and indinavir concent rations were often below or close to these target concentrations, particula rly when used as a single protease inhibitor. Concentration-controlled stud ies should now be used to select proper target concentrations for each prot ease inhibitor, either prescribed alone or in combination.