Zidovudine transport within the rabbit brain during intracerebroventricular administration and the effect of probenecid

Journal of Pharmaceutical Sciences
Y WangR J Sawchuk

Abstract

The elimination of zidovudine (AZT) from cerebrospinal fluid (CSF), its distribution from CSF to brain tissue, and its transport from brain extracellular fluid (ECF) to plasma were studied during intracerebroventricular (i.c.v.) infusion in unanesthetized rabbits. The effect of probenecid (PBD) on these transport processes was also studied. The concentration of AZT in brain ECF was measured by microdialysis with retrodialysis calibration for in vivo recovery. Plasma and CSF were sampled and analyzed for AZT and PBD using HPLC. The elimination of AZT from CSF showed nonlinear characteristics as the i.c.v. infusion rate was increased to 1 mg/h kg. The estimated maximum transport capacity and dissociation constant were 3.5 micrograms/min kg and 127 micrograms/mL, respectively. The total linear elimination clearance from CSF was 0.0073 mL/min kg. The spatial distribution of AZT in brain during i.c.v. infusion was simulated using a mathematical model which describes diffusive solute transport in brain ECF and efflux across the blood-brain barrier. This analysis yielded a brain to plasma efflux rate constant of 0.040/min. This parameter and the elimination clearance from CSF decreased significantly by the end of an 8-hour period duri...Continue Reading

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Citations

Jul 29, 1999·Biomedical Chromatography : BMC·C S Chaurasia
Aug 24, 2011·Cancer Chemotherapy and Pharmacology·Denise Campos-ArroyoJorge Melendez-Zajgla
Nov 20, 2012·CNS Drugs·Christine EisfeldIngo Husstedt
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Mar 11, 2016·Cancer Investigation·Denise Campos-ArroyoJorge Melendez-Zajgla
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Apr 18, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Guoyu PanWilliam F Elmquist
Nov 17, 2004·Reviews in Medical Virology·Nathalie Strazielle, Jean-François Ghersi-Egea
Jan 15, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ekram Ahmed ChowdhuryLuca Cucullo

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