Biomedical accelerator mass spectrometry: Recent applications in metabolism and pharmacokinetics

Lappin, Graham and Stevens, Lloyd (2008) Biomedical accelerator mass spectrometry: Recent applications in metabolism and pharmacokinetics. Expert Opinion on Drug Metabolism and Toxicology, 4 (8). pp. 1021-1033. ISSN 1742-5255

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Background: Accelerator mass spectrometry (AMS) is a sensitive isotope ratio technique used in drug development that allows for small levels of 14C-drug to be administered to humans, thereby removing regulatory hurdles associated with radiotracer studies. AMS uses innovative study designs to obtain pharmacokinetic and metabolism data. Objective: This review addresses the metabolism and pharmacokinetics relevant to cases where therapeutic drug concentrations are achieved in humans. Methods: The review focuses on two study designs: i) administration of tracer 14C-drug intravenously with a simultaneous non-labelled extravascular therapeutic dose to obtain the pharmacokinetic parameters of clearance, volume of distribution and absolute bioavailability without extensive intravenous toxicology safety studies or formulation development; and ii) use of low levels of 14C-drug during Phase I studies to investigate the quantitative metabolism of the drug in humans early in drug development, as required by the new FDA guideline issued in February 2008. Results/conclusions: Early knowledge about a drug's clearance, volume of distribution, absolute bioavailability and metabolism can affect the development of a new drug candidate. © 2008 Informa UK Ltd.

Keywords:carbon 14, drug, drug metabolite, erythromycin, excipient, fexofenadine, meloxicam, midazolam, nelfinavir, tolbutamide, tracer, zidovudine, accelerator mass spectrometry, area under the curve, clinical trial, dose response, drug bioavailability, drug blood level, drug clearance, drug design, drug determination, drug distribution, drug half life, drug labeling, drug metabolism, drug safety, food and drug administration, good manufacturing practice, human, intermethod comparison, isotope labeling, low drug dose, mass spectrometry, maximum plasma concentration, nonhuman, pharmacokinetics, quantitative analysis, radiosensitivity, reversed phase high performance liquid chromatography, review, Biological Availability, Carbon Radioisotopes, Clinical Trials, Phase I as Topic, Guidelines as Topic, Humans, Injections, Intravenous, Tissue Distribution, United States, United States Food and Drug Administration
Divisions:College of Science > School of Pharmacy
ID Code:8225
Deposited On:24 Mar 2013 16:13

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