title: Pharmacokinetics and extracellular distribution to blood, brain, and muscle of alovudine (3'-fluorothymidine) and zidovudine in the rat studied by microdialysis.
abstract: Microdialysis was applied to sample the free drug concentration in the extracellular fluid in brain, muscle, and blood of rats given alovudine (n = 6) (3'-fluorothymidine) or zidovudine (n = 5) (25 mg/kg s.c.). Alovudine and zidovudine were analyzed by means of high performance liquid chromatography (HPLC) with UV detection. The assay for zidovudine was validated by a radioimmunoassay. In addition, the plasma protein binding of the drugs was measured by microdialysis in vitro. The concentrations attained in blood and muscle were similar for each drug, with a Cmax of 57 microM (blood) and 54 microM (muscle) for alovudine and 38 and 46 microM, respectively, for zidovudine. In contrast the Cmax in brain was 8 microM for alovudine and 4 microM for zidovudine. The peak concentration was attained 20-40 min after injection in blood and muscle and 40-60 min after injection in the brain. The half-lives of zidovudine in both blood and muscle were 37 min and in brain 69 min. For alovudine the corresponding half-lives were significantly longer: 61, 58, and 105 min, respectively. The ratio of the AUC0-180 brain/blood was 0.257 for alovudine and 0.186 for zidovudine. The plasma protein binding of zidovudine was 10%, while alovudine was virtually unbound.
authors: Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
authors: L
authors: L
authors: Ståhle
authors: E
authors: E
authors: Guzenda
authors: E
authors: E
authors: Ljungdahl-Ståhle
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis / Q000379:methods; D015224:Dideoxynucleosides / Q000737:chemistry / Q000493:pharmacokinetics*; D005110:Extracellular Space / Q000378:metabolism; D007526:Isoelectric Point; D008297:Male; D008832:Microchemistry; D009132:Muscles / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014018:Tissue Distribution; D015215:Zidovudine / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D015224:Dideoxynucleosides; D015215:Zidovudine; C002854:alovudine