DISPOSITION OF DIADENOSINE 5',5'''-P-1,P-4-TETRAPHOSPHATE (AP4A) IN RATS

The disposition of diadenosine 5',5'''-P-1,P-4-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 mu g/ml and 4.32 mu g/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.