Pharmacokinetic modeling of hepatocyte growth factor in experimental animals and humans

Hepatocyte growth factor (HGF) is under development for treatment of renal failure. This study was designed to clarify changes in HGF pharmacokinetics in renal failure and to establish a pharmacokinetic model applicable to single and repeated doses. The plasma concentration profile in mice with glycerol-induced acute renal failure was similar to that in normal mice, indicating a minimal contribution of kidney to systemic clearance of HGF. Nevertheless, accumulation of fluorescein-4-isocyanate-labeled HGF in renal tubules in both cases suggests the occurrence of efficient endocytosis of HGF in kidney. A pharmacokinetic model including plasma and liver compartments was constructed, incorporating both high- and low-affinity receptors for association and subsequent endocytosis of HGF because HGF is eliminated via specific receptor c-Met and heparin-like substance. The model well explained the plasma concentration profiles at all doses examined after bolus injection in animals and humans, and those during infusion in rodents. It includes externalization of receptors, which is negatively regulated by HGF, and can explain the gradual increase in trough concentration during repeated dosing in monkeys. Overall pharmacokinetic profiles of HGF are governed by at least two receptors and are well described by this pharmacokinetic model, which should assist in safe management of clinical trials. © 2012 Wiley Periodicals, Inc

Field trial of primary and booster dose of inactivated vaccine against bovine respiratory bacteria in young Holstein calves

The objective of this research was to evaluate the antibody response to multiple doses of an inactivated mixed vaccine against Histophilus somni, Pasteurella multocida, and Mannheimia haemolytica, and to investigate the influence of age at time of vaccination in the field

Antibody response to 1.0 and 0.5 mL doses of an inactivated bacterial vaccine against bovine respiratory disease in young Holstein calves: a field trial

Early vaccination of cattle with an inactivated commercial bacterial vaccine against bovine respiratory disease has been reported to increase antibody production and can alleviate the disease. However, its dosage has been little investigated in young Holstein calves. This study addresses the need to establish guide values for vaccine dosage in these animals