Pharmacokinetics of the antiviral agent 3-deazaneplanocin A

Summary

The pharmacokinetics of 3-deazaneplanocin A (c³Nep), a competitive inhibitor of S-adenosyl-l-homocysteine (AdoHcy) hydrolase and novel antiviral agent, was investigated in female BALB/c mice. Animals were given a single intravenous dose of [³H]-c³Nep (0.1 mg/kg: 10 μCi), and blood and selected tissues were collected at various intervals thereafter for up to 72 h. The plasma concentration versus time data for c³Nep was best approximated by a two-compartment open model with first order elimination. The elimination half-life was 12.8 min, the area-under curve (AUC) was 3.38 μg.min.ml⁻¹. The distribution of c³Nep into tissues was not extensive. Following 30, 120 min, and 24 h after dosing, the kidneys and the liver contained the highest amount of drug, but this amount did not exceed 1 μg/g tissue. At these time periods, the majority of activity in the tissues represented labeled derivatives of c³Nep indicating that this compound was converted to stable metabolites. The presence of labeled conversion products in the blood confirmed that this drug is metabolized in vivo. The fact that c³Nep bound to plasma proteins in vitro may explain this drug’s limited tissue distribution. The half-life and tissue distribution of c³Nep were different from those of carbocyclic 3-deazaadenosine, a related adenosine nucleoside antiviral drug and AdoHcy hydrolase inhibitor.