title: Clinical use of a simultaneous HPLC assay for indinavir, saquinavir, ritonavir and nelfinavir in children and adults.
abstract: PROTEASE INHIBITOR TDM: This study examines the importance of therapeutic drug monitoring (TDM) of protease inhibitors (PI) in adults and children infected with the human immunodeficiency virus (HIV). Pediatric patients were included because information in this population is limited. A high performance liquid chromatographic (HPLC) assay measured indinavir, saquinavir, ritonavir and nelfinavir simultaneously in 0.2 mL of plasma. Initially, the reliability, sensitivity and specificity of the assay were verified in stored samples of plasma from adult patients who had been receiving PIs. Non-detectable concentrations (ND) were <25-50 ng/mL. In 96 out of 293 stored samples from adult patients, selected randomly, concentrations of PIs were ND. In a second prospective study of 10 adults (9 mothers and one father, aged 24-42 years) and 15 children (2.9-18 years) ND levels of PI were observed frequently (27% or 4 out of 15 pediatric subjects). In the latter study, drug-drug interactions, dosing errors, noncompliance and other important problems were identified and corrected. Routine monitoring and interpretation of PI concentrations (TDM) may improve the management of adult and pediatric patients infected with HIV, especially in those who fail to respond, develop adverse effects or viral resistance, or lack compliance.
authors.affiliation: Department of Pharmacology, The Ohio State University, and Divisions of Pharmacology/Toxicology and Infectious Diseases, Children's Hospital, Columbus, OH, USA.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Walson
authors.forename: Shareen
authors.initials: S
authors.lastname: Cox
authors.forename: Ilya
authors.initials: I
authors.lastname: Utkin
authors.forename: Nicholas
authors.initials: N
authors.lastname: Gerber
authors.forename: Linda
authors.initials: L
authors.lastname: Crim
authors.forename: Michael
authors.initials: M
authors.lastname: Brady
authors.forename: Katalin
authors.initials: K
authors.lastname: Koranyi
mesh_terms: D000328:Adult; D002648:Child; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D005260:Female; D017320:HIV Protease Inhibitors / Q000097:blood*; D006801:Humans; D019469:Indinavir / Q000097:blood*; D008297:Male; D019888:Nelfinavir / Q000097:blood*; D019438:Ritonavir / Q000097:blood*; D019258:Saquinavir / Q000097:blood*
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir