Interspecies scaling of clearance and volume of distribution for digoxin-specific Fab

Digoxin-specific Fab are recognized to be effective in the treatment of acute cardiac glycoside poisoning but no pharmacokinetic studies have been performed in human volunteers. We thuss propose an allometric approach among these mammalian species to predict Fab pharmacokineric parameters in humans. Plasma disposition of digoxin-specific Fab was studued at a 10 mg/kg iv dose in mice, rats and rabbits. Fab plasma concentration was determined by sensitive and specific radioimmunoassay. Allometric equations showed that the pharmacokinetik parameters (distribution volumes (V-c(ml)-=0.084W(0.96); Vd(ss)(ml)=0.24W(0.96); Vd-beta (ml)=0.55W(0.96), r(2)=1), total body clearance (Cl-tot(ml/hr)=0.61W(0.67), r(2)=0.999), and terminal half-life (t1/2-beta(hr)=0.63W(0.29)) correlated with body weight. The Fab plasma concentration-time data plotted as a complex Dedrick relationship were superimposable. Using these allometric techniques, Vd(ss), Vd-beta, Cl-tot and t1/2-beta were calculated as 10.75 liter, 24.64 liter, 17.9 ml/min, and 16hr, repectively, for a human subject of 70kg body weight. These values are in accordance with those previously described in digoxin-Fab-treated patients (body weight equals 61+/-3kg, Vd-beta=24.9+/-3.7 liter ; Cl-tot=20.8+/-2.1ml/min; t1/2-beta=14.3+/-1.8hr). Results indicate that the primary Fab pharmacokinetic paramaters can be reasonably estimated in man using pharmacokinetic data from three animal species.