(c) 2009 American Institute of Physics. [DOI: 10.1063/1.3177324]“
“Background: Information has been

very limited on the population pharmacokinetics (PK) of etomidate in pediatric patients. The purpose of this study AC220 concentration was to characterize the PK of etomidate in children.

Methods: Forty-nine children aged over 6 months undergoing elective surgery received etomidate 0.3 mg kg) 1 bolus i. v. within 15 s for anesthesia induction. Arterial blood samples were collected for 2 h after injection. A population nonlinear mixed effects modeling approach was used to characterize etomidate PK. Estimates were standardized to a 70-kg adult using allometric size models.

Results: Children had a median age of 4 years (0.53-13.21 years) and weight 15.7 kg (7.5-52 kg). PK of etomidate was best estimated using Volasertib a three-compartment model with weight on systemic

(Cl-1) and inter-compartmental clearances (Cl-2, Cl-3), central (V1), and peripheral compartment volumes (V-2, V-3). The most significant PK covariate was age, with increasing age having reduced size-adjusted Cl-1, V-1, and V-3 (all P < 0.01). The estimates of PK parameter (standardized to 70-kg adult) for a typical 4-yearold children were Cl-1 = 1.50 l min) 1, Cl-2 = 1.95 l min) 1, Cl-3 = 1.23 l min(-1), V-1 = 9.51 l, V-2 = 11.0 l, and V-3 = 79.2 l, respectively.

Conclusions: Owing to enhanced clearance and increased central compartment volume of etomidate, smaller (younger) children will require higher etomidate bolus dose than larger (older) children to achieve equivalent plasma concentrations. The dependence of Cl-1 and V-1 on age does not support weight-based etomidate dosing in smaller children.”
“Although interleukins

(IL) 8 and 10 predict lung viability in lung transplantation from heart beating donors (HBD) and IL-1 beta is a marker of ex vivo performance from after cardiac death donors (ACDD), IL expression in the recipient remains unknown. This study assessed IL-1 beta, IL-8 and IL-10 as indicators of functional performance in single-lung transplantation from ACDD pigs. Animals were divided into: (i) HBD: immediate lung excision; (ii) ACDD: fibrillation, 30 min warm ischemia and Captisol mouse 3 h topical cooling. Left lungs of both groups were then flushed with Perfadex and stored at 3-4 degrees C for 3 h. IL in bronchoalveolar lavage fluid (BAL) and hemodynamic and graft function were measured in the donor and during the 2 h reperfusion period in the recipient. Myeloperoxidase, nuclear factor kappa beta, wet/dry weight ratio and a histologic injury score were assessed from biopsies in basal conditions in the donor and at the end of reperfusion. Despite similar pulmonary function and histologic markers of injury in both groups and higher IL-1 beta in the donor of ACDD, IL-8 during reperfusion was significantly lower in ACDD (119 +/- 33% of basal) than in HBD (306 +/- 238%, P < 0.05) recipients.