PT  - JOURNAL ARTICLE
AU  - Jeri S. Roth
AU  - Cynthia M. McCully
AU  - Frank M. Balis
AU  - David G. Poplack
AU  - James A. Kelley
TI  - 2′-β-Fluoro-2′,3′-dideoxyadenosine, Lodenosine, in Rhesus Monkeys: Plasma and Cerebrospinal Fluid Pharmacokinetics and Urinary Disposition
DP  - 1999 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1128--1132
VI  - 27
IP  - 10
4099  - http://dmd.aspetjournals.org/content/27/10/1128.short
4100  - http://dmd.aspetjournals.org/content/27/10/1128.full
SO  - Drug Metab Dispos1999 Oct 01; 27
AB  - 2′-β-Fluoro-2′,3′-dideoxyadenosine (F-ddA, lodenosine) is a nucleoside analog that was rationally designed as a more chemically and enzymatically stable anti-AIDS drug than its parent compound 2′,3′-dideoxyadenosine or didanosine. Plasma and cerebrospinal fluid (CSF) pharmacokinetics of this compound and its major metabolite, 2′-β-fluoro-2′,3′-dideoxyinosine (F-ddI), were studied in three rhesus monkeys after a single 20 mg/kg dose administered as an i.v. push. F-ddA exhibited a mean residence time of 0.17 h in plasma and its plasma concentration time profile appeared to be biexponential. The majority of plasma exposure was from F-ddI, with a mean parent drug area under the curve (AUC) to metabolite AUC ratio of 0.16. CSF levels were low, with a mean CSF AUC to plasma AUC ratio of 0.068, with approximately one-quarter of this exposure in CSF due to unchanged drug. Urinary excretion accounted for half of the drug administered with the majority recovered as the metabolite, F-ddI. In a separate experiment, one monkey received a 20 mg/kg i.v. dose of F-ddI. The total dideoxynucleoside plasma exposure was greater than it was after administration of F-ddA; however, the CSF AUC to plasma AUC ratio was a factor of 4 lower (0.017). Thus, F-ddA central nervous system penetration is at least comparable to that of didanosine, indicating that this experimental drug has potential as an addition to currently approved AIDS therapies. U.S. Government