Preparation and pharmacokinetics of 11C labeled stavudine (d4T)

Nuclear Medicine and Biology
Eli LivniAlan J Fischman

Abstract

Stavudine, a potent antiviral agent for treating human immunodeficiency virus (HIV) infections, was radiolabeled with (11)C by methylation of a specifically designed precursor, 5'-O-(2-tetrahydropyranyl)-5-bromo-2',3'-didehydro-3'-deoxythymidine, with (11)C H(3)I. The radiolabeled drug was isolated by reverse phase HPLC. A total time of approximately 45 minutes was required for synthesis, purification and isolation of (11)C stavudine with chemical and radiochemical purities of greater than 98%. (11)C stavudine was combined with unlabeled drug (2.0 mg/kg) and used to study its pharmacokinetics in rats by measurement of radioactivity in excised tissues. In this species, there was rapid accumulation of drug in all tissue. In all tissues, with the exceptions of testis and brain, highest concentrations of drug were detected at 5 minutes after injection and decreased monotonically thereafter. The peak concentration (microg/g) of stavudine in blood was 1.78 +/- 0.16 and similar levels were achieved in most other tissues; heart 1.66 +/- 0.11, lung 1.60 +/- 0.15, liver 2.13 +/- 0.17, spleen 1.61 +/- 0.15, adrenal 1.47 +/- 0.20, stomach 1.40 +/- 0.11, GI tract 1.44 +/- 0.14, skeletal muscle 1.38 +/- 0.15 and bone 1.30 +/- 0.16. Much high...Continue Reading

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Citations

Aug 12, 2009·Antimicrobial Agents and Chemotherapy·Michele Di MascioDale Kiesewetter
Nov 22, 2014·The Journal of Infectious Diseases·Laurent HouzetNathalie Dejucq-Rainsford
Aug 17, 2010·Antiviral Research·Mike BrayElaine Jagoda
Nov 24, 2007·Gynécologie, obstétrique & fertilité·A Le Tortorec, N Dejucq-Rainsford
Jun 18, 2009·International Journal of Andrology·A Le Tortorec, N Dejucq-Rainsford
Jul 3, 2020·Human Vaccines & Immunotherapeutics·Mariangela Cavarelli, Roger Le Grand
Jun 2, 2021·The Journal of Organic Chemistry·Cloudius R SagandiraPaul Watts

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