Pharmacokinetic monitoring of HIV-1 protease inhibitors in the antiretroviral therapy.
Combination therapy with protease inhibitors (PIs) is used for the treatment of patients infected with the human immunodeficiency virus (HIV). To achieve optimal drug concentrations for viral suppression and avoidance of drug toxicity, therapeutic drug monitoring of PIs levels has been considered essential. In this study an analytical procedure for simultaneous monitoring the plasma concentrations of a total four protease inhibitors: indinavir, lopinavir, nelfinavir and saquinavir was presented. The plasma samples were liquid/liquid extracted and subjected to high performance liquid chromatography (HPLC) analysis. The lopinavir and saquinavir in the patient plasma samples were monitored by ultraviolet detection at 215 nm. Extraction procedure using methyl tert-butyl ether and the mobile phase consisted from acetonitrile with phosphate buffer on a Symmetry C18 column were used to monitor these two compounds. Linearity of the method was obtained in the concentration range of 0.1 - 15.0 mg/mL for all four protease inhibitors. Under steady state conditions, the plasma concentrations of protein inhibitors in 23 patients were determined and area under the plasma concentration-time curve was estimated to maintain optimal viral suppression. We developed a simple and specific method for the simultaneous determination of lopinavir and saquinavir.
Department of Drug Chemistry, Faculty of Pharmacy, Medical University of Warsaw, Warsaw, Poland.
Tomasz
T
Pawiński
Piotr
P
Pulik
Beata
B
Gralak
Andrzej
A
Horban
D000328:Adult; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004338:Drug Combinations; D016903:Drug Monitoring / Q000379:methods*; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D019469:Indinavir / Q000097:blood / Q000493:pharmacokinetics; D061466:Lopinavir; D008875:Middle Aged; D019888:Nelfinavir / Q000097:blood / Q000493:pharmacokinetics; D011744:Pyrimidinones / Q000097:blood / Q000493:pharmacokinetics; D019258:Saquinavir / Q000097:blood / Q000493:pharmacokinetics
D004338:Drug Combinations; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019469:Indinavir; D019888:Nelfinavir; D019258:Saquinavir