Pharmacokinetics and Bioavailability of 2-Amino-6-Cyclopropylamino-9-(2,3-Dideoxy-β-D-glyceropent-2-enofuranosyl) Purine (Cyclo-D4G) in Rats

Abstract

Abstract: Aim To characterize the pharmacokinetics of 2-amino-6-cyclopropylamino-9-(2,3-dideoxy-β-D-glyceropent-2-enofuranosyl) purine (Cyclo-D4G) following intravenous administration and oral administration to rats. Methods The concentrations of Cyclo-D4G in rat (Sprague-Dawley male rats) plasma and urine were analyzed by high performance liquid chromatography (HPLC). Results Following intravenous administration to rats, concentrations of Cyclo-D4G in plasma declined with a terminal phase half-life of 0.78±0.14 h (x±s).Total clearance was 0.90±0.21 L·h^-1·kg^-1. Renal excretion of unchanged Cyclo-D4G accounted for approximately 20% of total clearance.Steady state volume of distribution was 0.91±0.07 L·kg^-1. After oral administration to rats, concentrations of Cyclo-D4G in plasma declined with a terminal phase half-life of 0.83±0.13 h (x±s).Total clearance was 3.81±2.03 L·h^-1·kg^-1. Renal excretion of unchanged Cyclo-D4G accounted for approximately 9% of total clearance.Oral bioavailability of Cyclo-D4G in rat was 26.9%. Conclusion The favorable pharmacokinetic profiles and lower toxicity provide support for further development of Cyclo-D4G clinical trials.

Key words: pharmacokinetics, pharmacokinetics, bioavailability, bioavailability, HPLC analysi s, HPLC analysi s, D4G prodrug, D4G prodrug

CLC Number:

R969.1

R917.797

Supporting:

LIU Yi, YANG Zhen-jun^*, BOUDINOT F.Douglas, CHU Chung Kuang, ZHANG Li-he . Pharmacokinetics and Bioavailability of 2-Amino-6-Cyclopropylamino-9-(2,3-Dideoxy-β-D-glyceropent-2-enofuranosyl) Purine (Cyclo-D4G) in Rats[J]. .

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