Pharmacokinetics of Alacramyn^®in healthy individuals

^{1Vázquez, H.; 2Chávez-Haro, A.; 1García-Ubbelohde, W. and 3Alagón, A.}

1 Laboratorios Silanes, México; 2 Servicio de Urgencias de la Clínica H.G.Z. T1 No 21, León, México; 3 Instituto de Biotecnología-UNAM, Cuernavaca, México.

Intravenous (IV) administration of highly purified F(ab’)2 fragments obtained from plasma of hyperimmunized horses (Alacramyn^®) constitutes the cornerstone of the therapy of more than 100,000 patients per year envenomed by Centruroides scorpions in Mexico. However, nothing was known of plasma concentration profiles, tissue distribution, and elimination of Alacramyn^® in humans. Pharmacokinetic parameters were derived from the serum antivenom concentration-time data of 6 men and 2 women who received a single IV dose of antivenom (47.5 mg of protein). The median (range) age and weight of the volunteers was 24.5 years (18-26) and 74.5 kg (48-150). Serum samples were collected at 0, 5, 15, 30, 45, 60, 90 min, and at 2, 3, 6, 24, 72, 96, 240 and 504 hr after injection of antivenom. A sandwich ELISA was used to measure the F(ab’)2 fragments concentration in the serum samples. Plasma concentrations of antivenom at various times after IV injection were analyzed by the PK Solutions 2.0 software (Summit Research Services, Montrose, CO, USA). In all patients plasma concentrations of antivenom after administration showed a better fitting to a triexponential decline than to a biexponential one, compatible with a three-compartment model. This model includes a central compartment (blood), a rapid equilibrating ‘shallow’ tissue compartment and a slowly equilibrating ‘deep’ tissue compartment. The antivenom had a rapid initial distribution phase with a half-life of 0.24 hr (0.12-0.52) and an intermediate phase of distribution with a half-life of 13.2 hr (6.7-34.0); its elimination half-life was 138.6 hr (84.0-222.8); its volume of distribution was 223.5 ml/kg (119.7-314.4) and its clearance 1.02 ml/hr/kg (0.47-1.74).

Correspondence to: hvazquez@ibt.unam.mx