Clinical use of a simultaneous HPLC assay for indinavir, saquinavir, ritonavir, and nelfinavir in children and adults.
Protease inhibitor (PI) monitoring may improve the care of human immunodeficiency virus (HIV)-infected patients; however, pediatric data are limited. A high-performance liquid chromatographic (HPLC) assay developed for the simultaneous determination of indinavir, ritonavir, saquinavir, and nelfinavir in 0.2 mL of plasma was used to quantify PI concentrations in HIV patients. The reliability, sensitivity, and specificity of the assay were first verified in stored adult samples. Later, blood collected prospectively from patients aged 2.9 to 42 years of age (10 adults aged 24 to 42 and 15 children aged 2.9 to 18 years) was tested. Nondetectable (below 25-50 ng/mL) concentrations (ND) were found in 33% of adult samples and 24% of pediatric samples. Four patients taking from 13.7 to 28 mg/kg/d of ritonavir (mean of 21.3) had concentrations ranging from ND to 11.4 microg/mL, quite different from predicted values. Correctable, important clinical problems including drug-drug interactions, drug administration problems, and confirmed noncompliance were identified and corrected using modern therapeutic drug monitoring (TDM) techniques. Routine PI monitoring and interpretation (TDM) could improve the care of adult and pediatric HIV patients; especially in patients who do not respond as expected to treatment, develop viral resistance or toxicity, and have questionable compliance.
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring; D017320:HIV Protease Inhibitors / Q000097:blood*; D006801:Humans; D019469:Indinavir / Q000097:blood; D019888:Nelfinavir / Q000097:blood; D019438:Ritonavir / Q000097:blood; D019258:Saquinavir / Q000097:blood
D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir