Pharmacokinetics of Vipera aspis venom after experimental envenomation in rabbits

Abstract

Toxicokinetic studies of Vipera aspis venom were performed in rabbits after experimental envenomation. Venom proteins with a molecular weight greater than 6 kDa (high-molecular weight proteins) and which reacted in enzyme-linked immunosorbent assay with specific antiviper venom Fab'2, were also responsible for the lethal potency and the capillary permeability increasing activity of the venom. Conversely, low-molecular weight proteins were not detected by enzyme-linked immunosorbent assay and were pharmacologically inactive. The toxicokinetics of both classes of venom components were studied, using high-molecular weight and low-molecular weight radiolabeled proteins as well as enzyme-linked immunosorbent assay. After intravenous injection, Vipera aspis venom in plasma followed a biexponential decline with a distribution half-life of 0.7 hr and an elimination half-life of 12 hr. The distribution volume was 1.2 l.kg-1 and the systemic clearance was 84 ml.hr-1.kg-1. Venom levels in plasma after intramuscular injection of three doses (300, 500 and 700 micrograms/kg) of venom increased within the few hours after the venom administration to reach maximal values proportional to the injected doses. They subsequently followed a monoexponential decline, with an apparent terminal half-life of 32.5 hr. Absorption was a kinetically complex process, rapid during the first 24 hr and continued at a slower rate over the subsequent 72 hr. Bioavailability of venom was about 65%, regardless of the administered dose, and less than 5% of venom injected was excreted by the renal route.