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
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.