Clinical Pharmacology Unit (UPC)
Population Pharmacokinetics of Intravenous Pantoprazole in Pediatric Intensive Care Patients
Aims
To characterize the pharmacokinetics of intravenous pantoprazole in a pediatric intensive care population and determine the influence of demographic factors, systemic inflammatory response syndrome (SIRS), hepatic dysfunction and concomitantly used CYP2C19 inducers and inhibitors on the drug’s pharmacokinetics.
Methods
A total of 156 pantoprazole concentration measurements from 20 patients (10 days to 16.4 years of age) at risk for or with upper gastrointestinal bleeding, who received pantoprazole doses ranging from 19.9 to 140.6mg/1.73m2/day, were analyzed using noncompartmental and nonlinear mixed effect modeling approaches.
Results
The noncompartmental results showed that median clearance (CL), volume of distribution and elimination half-life were 0.14 L/h/kg, 0.20 L/kg and 1.7 h, respectively. The best structural model for pantoprazole was a two-compartment model with zero order infusion and first order elimination. Body weight, SIRS, age, hepatic dysfunction and presence of CYP2C19 inhibitors were significant covariates affecting CL, accounting for 75% of interindividual variability. Only body weight significantly influenced central volume of distribution (Vc). In the final model, the estimated CL and Vc were 5.28 L/h and 2.22 L, respectively, for a typical 5-year-old child weighing 20 kg. Pantoprazole CL increased with weight and age while the presence of SIRS, CYP2C19 inhibitors and hepatic dysfunction, when present separately, significantly decreased pantoprazole CL by 62.3%, 65.8% and 50.5%, respectively.
Conclusion
These results provide important information for physicians regarding the selection of a starting dose and dosing regimen of pantoprazole for pediatric intensive care patients based on factors frequently encountered in this population.