The application of accelerator mass spectrometry to absolute bioavailability studies in humans: Simultaneous administration of an intravenous microdose of 14C-nelfinavir mesylate solution and oral nelfinavir to healthy volunteers

Sarapa, Nenad, Hsyu, Poe-Hirr, Lappin, Graham and Garner, Ronald Folin (2005) The application of accelerator mass spectrometry to absolute bioavailability studies in humans: Simultaneous administration of an intravenous microdose of 14C-nelfinavir mesylate solution and oral nelfinavir to healthy volunteers. Journal of Clinical Pharmacology, 45 (10). pp. 1198-1205. ISSN 0091-2700

Full content URL: http://dx.doi.org/10.1177/0091270005280051

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Item Type:Article
Item Status:Live Archive

Abstract

The absolute bioavailability of nelfinavir was determined in 6 healthy volunteers following simultaneous administration of 1250 mg oral nelfinavir and an intravenous infusion of 14C-nelfinavir mesylate on day 1 and at steady state. Nelfinavir oral bioavailability decreased from 0.88 to 0.47 over the 11-day study period. The moderate bioavailability of nelfinavir was due to significant first-pass metabolism rather than low absorption, limiting the potential of formulation improvement to decrease pill burden. Human absolute bioavailability studies with accelerator mass spectrometry microdosing, in which an intravenous microdose is given along with a conventional oral dose of the same drug, can differentiate between gastrointestinal absorption and the first-pass metabolism of new drug candidates. Accelerator mass spectrometry allowed a several thousand-fold dose reduction of 14C-nelfinavir relative to that required for liquid scintillation counting. Accelerator mass spectrometry microdosing reduces potential safety issues around dosing radioactivity to humans and prevents the need to formulate high intravenous doses. ©2005 the American College of Clinical Pharmacology.

Keywords:ag 1402, carbon 14, cholesterol, drug metabolite, nelfinavir, triacylglycerol, unclassified drug, adult, area under the curve, article, cholesterol blood level, clinical trial, diarrhea, drug absorption, drug bioavailability, drug blood level, drug clearance, drug half life, drug safety, drug structure, first pass effect, human, human experiment, liquid scintillation counting, male, mass spectrometry, multiple drug dose, normal human, open study, reversed phase high performance liquid chromatography, statistical analysis, steady state, tablet, triacylglycerol blood level, volunteer, Administration, Oral, Adolescent, Adult, Area Under Curve, Biological Availability, Carbon Radioisotopes, HIV Protease Inhibitors, Humans, Infusions, Intravenous, Metabolic Clearance Rate, Middle Aged, Reproducibility of Results, Time Factors
Divisions:College of Science > School of Pharmacy
ID Code:8236
Deposited On:24 Mar 2013 15:55

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