Simple, rapid and sensitive high-performance liquid chromatographic determination of delavirdine and its N-desisopropyl metabolite in human plasma

Staton, Brian A.; Johnson, Marie; Friis, Janice M.; Adams, Wade J.

doi:10.1016/0378-4347(95)00045-k

Cited by 27 publications

(8 citation statements)

References 3 publications

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“…Plasma samples from the second study were analyzed for both delavirdine and N-desisopropyl delavirdine by Covance Laboratories Inc (Madison, Wis) with the use of an HPLC assay with fluorescence detection as previously described. 39 Calibration curves were linear over the concentration range of 0.22 to 55 mol/L for both analytes. Interassay precision, expressed as relative SD, ranged from 2.4% to 7.1% for delavirdine and 3.3% to 3.5% for N-desisopropyl delavirdine.…”

Section: Analytic Methodsmentioning

confidence: 89%

Pharmacokinetic interaction between amprenavir and delavirdine: Evidence of induced clearance by amprenavir

Tran

2002

Clinical Pharmacology & Therapeutics

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Because of the inhibitory effect of delavirdine on the cytochrome P450 3A4-mediated metabolism of amprenavir, the combination of a reduced dose of amprenavir, 600 mg twice daily, with delavirdine resulted in a higher amprenavir exposure than the standard dose of amprenavir, 1200 mg twice daily. However, amprenavir induced the clearance of delavirdine, resulting in a reduction in delavirdine exposure. Further clinical studies are needed to determine the appropriate dosing regimens for delavirdine and amprenavir during coadministration.

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Section: Analytic Methodsmentioning

confidence: 89%

Pharmacokinetic interaction between amprenavir and delavirdine: Evidence of induced clearance by amprenavir

Tran

2002

Clinical Pharmacology & Therapeutics

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“…The sampling for pharmacologic studies, dose alteration, and repeat sampling usually took place within 7 to 14 days. Delavirdine concentrations were measured by a validated high-pressure liquid chromatography assay in the Laboratory for Antiviral Research, State University of New York at Buffalo, by a method developed by the Pharmacia & Upjohn Co. (17).…”

Section: Methodsmentioning

confidence: 99%

ACTG 260: a Randomized, Phase I-II, Dose-Ranging Trial of the Anti-Human Immunodeficiency Virus Activity of Delavirdine Monotherapy

Para

Meehan

Holden‐Wiltse

et al. 1999

Antimicrob Agents Chemother

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ACTG 260 was an open-label, four-arm trial designed to study the safety and anti-human immunodeficiency virus (anti-HIV) activity of delavirdine monotherapy at three ranges of concentrations in plasma compared to those of control therapy with zidovudine or didanosine. Delavirdine doses were adjusted weekly until subjects were within their target trough concentration range (3 to 10, 11 to 30, or 31 to 50 M). A total of 113 subjects were analyzed. At week 2, the mean HIV type 1 (HIV-1) RNA level declines among the subjects in the three delavirdine arms were similar (0.87, 1.08, and 1.02 log 10 for the low, middle, and high target arms, respectively), but by week 8, the subjects in the pooled delavirdine arms showed only a 0.10 log 10 reduction. In the subjects in the nucleoside arm, mean HIV-1 RNA level reductions at weeks 2 and 8 were 0.67 and 0.55 log 10 , respectively. Because viral suppression by delavirdine was not maintained, the trial was stopped early. Rash, which was usually self-limited, developed in 36% of subjects who received delavirdine. Delavirdine monotherapy has potent anti-HIV activity at 2 weeks, but its activity is time limited due to the rapid emergence of drug resistance.

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“…The samples are processed and the corresponding dosing information is entered into a database. The plasma samples are then shipped to the analytical laboratory for determination of delavirdine plasma concentrations using validated HPLC methods (14,15). The completed assay results are appended to the corresponding dosing records and electronically transferred to the central data warehouse for analysis.…”

Section: System For Automated Drug Concentration Screeningmentioning

confidence: 99%

An Automated Drug Concentration Screening and Quality Assurance Program for Clinical Trials

et al. 1999

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The collection and analysis of drug concentration data collected during clinical trials is growing in popularity as a mechanism for explaining variability in patient outcomes. This paper describes an automated drug concentration screening and quality assurance program to monitor the acquisition of drug dosing information and concentration time data during clinical trials. This program serves to expedite the data cleaning process, allows for monitoring of possible concentration-related safety events, screens for drugdrug interactions during the execution of clinical trials, and provides the ability to produce interim, blinded reports to the sponsor and the data safety monitoring board. The goal of this paper is to describe the operation of the program as it has been used in practice and to highlight its benefits in the development program for delavirdine mesylate, a nonnucleoside reverse transcriptase inhibitor recently approved for the treatment of H N infection.

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Simple, rapid and sensitive high-performance liquid chromatographic determination of delavirdine and its N-desisopropyl metabolite in human plasma

Cited by 27 publications

References 3 publications

Pharmacokinetic interaction between amprenavir and delavirdine: Evidence of induced clearance by amprenavir

Pharmacokinetic interaction between amprenavir and delavirdine: Evidence of induced clearance by amprenavir

ACTG 260: a Randomized, Phase I-II, Dose-Ranging Trial of the Anti-Human Immunodeficiency Virus Activity of Delavirdine Monotherapy

An Automated Drug Concentration Screening and Quality Assurance Program for Clinical Trials

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