746   Intracellular Carbovir Triphosphate (CBVTP) Levels among Patients Taking Abacavir (ABC) Once Daily.

M. Harris*¹, S. Jutha¹, D. Back², S. Kewn², R. Marina³, and J. S. G. Montaner¹.
¹I. B. C. Ctr. for Excellence in HIV/ AIDS, Vancouver, British Columbia, Canada;²Univ. of Liverpool, Liverpool, UK; and³Glaxo Wellcome Inc., Missisauga, Ontario, Canada.

Background:Relatively long intracellular half-lives of active triphosphate metabolites support once daily dosing of nucleoside analogues such as ddI and 3TC. The standard dose of ABC is 300 mg twice daily, and previous work has shown a mean CBVTP concentration of 100 fmol/10⁶cells 12 hours after a 300 mg ABC dose. No data are available for intracellular levels of the active nucleotide CBVTP among patients taking ABC 600 mg once daily.

Methods:Six HIV-positive patients taking ABC 600 mg once daily as part of a stable (>30 days) combination regimen consented to participate. Blood samples were drawn at trough (24 hours after the previous ABC dose) and 1, 12, 14-16, 18, 20, 22, and 24 hours following an observed 600 mg ABC dose. After cell extraction, CBVTP and endogenous dGTP levels were determined in the extracts by enzymatic primer extension assays.

Results:Five men and one woman had been taking ABC 600 mg daily for 5-17 months (median 7). Results for the first 4 patients are shown below.

The half-life of CBVTP was estimated to be >12 hours.

Conclusions:Preliminary results of 24-hour CBVTP concentrations support the use of once daily ABC. Further studies are needed.