Disposition of Diadenosine 5′,5‴-P¹,P⁴-Tetraphosphate (Ap4A) in Rats

The disposition of diadenosine 5′, 5‴-P¹, P⁴-tetraphosphate (Ap4A), an endogenous dinucleotide, was investigated in rats. The degradation of Ap4A in rat plasma was very rapid and could be explained by a Michaelis-Menten equation : K_m and V_max values were 1.69 μg/ml and 4.32 μg/min/ml, respectively. Ap4A was degraded in rat plasma to ATP and AMP, but not to 2 ADP molecules, and these nucleotides were further degraded through adenosine. The degradation kinetics were examined. After intravenous bolus injection, Ap4A in plasma declined rapidly and the rate of elimination was dose-dependent : the biological half-life was about 3s at the dose of 1 mg/kg and was longer at 3 mg/kg. When Ap4A was administered by intravenous infusion (0.5 or 1.0 mg/kg/min), the plasma level rapidly reached a steady-state, which then rapidly declined after stopping the infusion.