The comparison of the pharmacokinetics of a low molecular weight heparin in the newborn and adult pig.
Standard heparin (SH) is frequently used in the sick neonate to prevent catheter related thrombosis. SH can cause significant bleeding complications in the adult and its use in the neonate is linked to an increased incidence of intraventricular hemorrhage. Recently available low molecular weight heparins (LMWH) offer potential advantages over SH in the adult by exhibiting a longer half life and decreased bleeding side effects compared to SH. Whether LMWHs would offer similar therapeutic advantages to the sick neonate is unknown. Using the porcine model of neonatal hemostasis we measured the pharmacokinetics of a LMWH (Choay 222) in the pig (ATIII level: 100%), in the piglet (ATIII level:50% of adult) and in the piglet given exogenous ATIII. All pigs were bolused with 125I-LMWH (5, 25 or 100 anti-factor Xa units/kg) and blood samples collected for the measurement of 125I-radioactivity, and anti-factor Xa activity. The half life of LMWH, measured as either 125I-radioactivity or as anti-factor Xa activity, was not dose dependent and was similar in pigs and piglets; however, the volume of distribution was greater in the piglet resulting in an increased total clearance compared to the pig. As well, the supplementation of the piglet with exogenous ATIII did not influence the pharmacokinetics of LMWH. The half life of the LMWH in both pigs and piglets was approximately twice as long as previously reported values for SH in the same animal model. Thus the longer half life of LMWH in the piglet, and the similarity of the half life in piglets and pigs suggest that LMWH may have a therapeutic advantage in the newborn over SH.
Andrew
M
M
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Ofosu
F
F
Brooker
L
L
Buchanan
M R
MR
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D000990:Antithrombin III / Q000494:pharmacology; D001780:Blood Coagulation Tests; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight / Q000493:pharmacokinetics*; D008433:Mathematics; D008657:Metabolic Clearance Rate; D010314:Partial Thromboplastin Time; D013552:Swine
D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D000990:Antithrombin III