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Alfentanil pharmacokinetics in piglets with increased intra-abdominal pressure
P J Davis1, R L Stiller, C M Roeber
1Department of Anaesthesiology, Children's Hospital of Pittsburgh, Pa.
Insights
Increased intra-abdominal pressure (IAP) in children does not significantly alter alfentanil pharmacokinetics. This finding is crucial for managing drug therapy in critically ill pediatric patients with elevated IAP.
Area of Science:
- Pediatric critical care medicine
- Pharmacology
- Anesthesiology
Background:
- Increased intra-abdominal pressure (IAP) is common in pediatric patients with end-stage liver disease, ascites, and post-surgical conditions like diaphragmatic hernia, omphalocele, gastroschisis, and liver transplantation.
- While hemodynamic effects of IAP are known, its impact on drug pharmacokinetics, distribution, and elimination remains poorly understood.
Purpose of the Study:
- To investigate the effects of experimentally increased intra-abdominal pressure on the pharmacokinetics of alfentanil in a pediatric animal model.
- To determine if elevated IAP significantly alters key pharmacokinetic parameters such as volume of distribution, mean residence time, and elimination half-life.
Main Methods:
- Pharmacokinetic study conducted in piglets subjected to experimentally induced increased intra-abdominal pressure (20 mm Hg).
- Alfentanil pharmacokinetics were analyzed and compared between piglets with elevated IAP and a control group of piglets without increased IAP.
Main Results:
- No significant differences were observed in the volume of distribution between the increased IAP group (0.46 +/- 0.06 L/kg) and the control group (0.61 +/- 0.23 L/kg).
- Mean residence time (68.8 +/- 27.8 min vs. 62.3 +/- 27.8 min) and elimination half-life (47.7 +/- 19.0 min vs. 43.2 +/- 19.3 min) also showed no significant alterations due to increased IAP.
Conclusions:
- Experimentally increased intra-abdominal pressure to 20 mm Hg does not appear to significantly affect the volume of distribution, mean residence time, or elimination half-life of alfentanil in piglets.
- These findings suggest that IAP may not be a major factor influencing alfentanil pharmacokinetics in pediatric patients, potentially simplifying drug dosing in this population.
Abstract:
Increased intra-abdominal pressure (IAP) occurs in pediatric patients with end-stage liver disease and ascites, as well as in children following surgery for diaphragmatic hernia, omphalocele, gastroschisis and orthotopic liver transplantation. Although the hemodynamic response to increased IAP is well described, little information is available regarding the effects of IAP on drug distribution and elimination. We studied the effects of increased IAP (20 mm Hg) on the pharmacokinetics of alfentanil in piglets and compared these findings with those in control animals. Increased IAP appears to have no significant effect on the volume of distribution (0.46 +/- 0.06 vs. 0.61 +/- 0.23 liter/kg), mean residence time (68.8 +/- 27.8 vs. 62.3 +/- 27.8 min) and elimination half-life (47.7 +/- 19.0 vs. 43.2 +/- 19.3 min).