Tolazoline pharmacokinetics in lambs.
Tolazoline has often been administered experimentally to lambs without consideration of its pharmacokinetics. We have used a chemically specific assay to determine tolazoline pharmacokinetic parameters in lambs after pulse and infusion doses: alpha = 0.184 +/- 0.046 (min-1), beta = 0.010 (pulse) and 0.0098 (infusion) +/- 0.0010 (min-1), Vdarea = 2534 +/- 688 ml/kg (pulse), and Vdss = 2890 +/- 342 ml/kg (infusion). The following doses can be used to reach steady-state plasma tolazoline concentrations: loading dose (microgram/kg) = 2890 X desired concentration (microgram/ml); infusion rate (microgram/kg X min) = 2890 (.010) X desired concentration (microgram/ml). These doses were used to produce 68 steady-state concentrations from 0.25 to 10.0 micrograms/ml. Clearances at steady state averaged 166 ml/min or 27.1 ml/min X kg at 2-17 days but increased markedly by 4 weeks of age. Using these doses, tolazoline-receptor interactions can be studied at constant plasma concentrations that approximate constant receptor concentrations.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D007700:Kinetics; D012756:Sheep; D014043:Tolazoline / Q000097:blood / Q000378:metabolism*
D014043:Tolazoline