BACKGROUND: The preterm infant is at risk for consumptive coagulopathy and thrombosis due to late maturation of coagulation regulatory proteins. Replacement proteins are available, but neonatal pharmacokinetic data are lacking. OBJECTIVE: The objective was to determine the pharmacokinetic properties of antithrombin (AT) and protein C (PC) in order to provide data for estimating doses in human infants. METHODS: A catheterized ovine model was used to determine pharmacokinetic properties of AT and PC, including plasma recovery, volume of distribution (V(d)), clearance (Cl) and half-life (t((1/2))), in the fetal lamb relative to the ewe. RESULTS: AT studies showed statistically significant differences between ewes and fetuses in recovery (p < 0.0001), V(d) (p = 0.0002) and Cl (p < 0.0001). The AT t((1/2)) was significantly shortened among fetuses (5.55 h, 95% CI: 4.01-7.08) compared to ewes (18.7 h, 95% CI: 11.6-25.8). PC recovery (p < 0.0001), V(d) (p < 0.0001) and Cl (p = 0.004) differed significantly between ewes and singleton fetuses as did the t((1/2)): 3.86 h (95% CI: 3.35-4.36) and 11.9 h (95% CI: 10.9-12.9) in the singletons and ewes, respectively. All PC parameters were significantly different for twins compared to ewes. CONCLUSIONS: AT and PC show decreased recovery and t((1/2)) in the fetal lamb. These data can be used to estimate dosing for human neonates in comparison with human adult dosing recommendations. (c) 2008 S. Karger AG, Basel.
BACKGROUND: The preterm infant is at risk for consumptive coagulopathy and thrombosis due to late maturation of coagulation regulatory proteins. Replacement proteins are available, but neonatal pharmacokinetic data are lacking. OBJECTIVE: The objective was to determine the pharmacokinetic properties of antithrombin (AT) and protein C (PC) in order to provide data for estimating doses in humaninfants. METHODS: A catheterized ovine model was used to determine pharmacokinetic properties of AT and PC, including plasma recovery, volume of distribution (V(d)), clearance (Cl) and half-life (t((1/2))), in the fetal lamb relative to the ewe. RESULTS: AT studies showed statistically significant differences between ewes and fetuses in recovery (p < 0.0001), V(d) (p = 0.0002) and Cl (p < 0.0001). The AT t((1/2)) was significantly shortened among fetuses (5.55 h, 95% CI: 4.01-7.08) compared to ewes (18.7 h, 95% CI: 11.6-25.8). PC recovery (p < 0.0001), V(d) (p < 0.0001) and Cl (p = 0.004) differed significantly between ewes and singleton fetuses as did the t((1/2)): 3.86 h (95% CI: 3.35-4.36) and 11.9 h (95% CI: 10.9-12.9) in the singletons and ewes, respectively. All PC parameters were significantly different for twins compared to ewes. CONCLUSIONS: AT and PC show decreased recovery and t((1/2)) in the fetal lamb. These data can be used to estimate dosing for human neonates in comparison with human adult dosing recommendations. (c) 2008 S. Karger AG, Basel.
Authors: D Menache; J P O'Malley; J B Schorr; B Wagner; C Williams; B M Alving; J O Ballard; S H Goodnight; W E Hathaway; M B Hultin Journal: Blood Date: 1990-01-01 Impact factor: 22.113
Authors: M J Manco-Johnson; S Spedale; M Peters; S F Townsend; L J Jacobson; J Christian; S D Krugman; W W Hay; J W Sparks Journal: Pediatr Res Date: 1995-03 Impact factor: 3.756
Authors: M Dreyfus; M Masterson; M David; G E Rivard; F M Müller; W Kreuz; T Beeg; A Minford; J Allgrove; J D Cohen Journal: Semin Thromb Hemost Date: 1995 Impact factor: 4.180