Clinical Pharmacokinetics and Population Pharmacokinetic Analysis of Voriconazole in Transplant Patients

摘要: Transplant patients at high risk of invasive mold infections receive voriconazole for prophylaxis. Large variability in exposure with a fixed dosing regimen was observed. Low predisposes infection. High concentrations are associated toxicity.The objectives to characterize the pharmacokinetics transplant patients, identify factors pharmacokinetics, and develop adequate guidelines patients.Liver, lung pediatric bone marrow (BMT) were enrolled. Multiple blood samples collected within one interval (totally 75 full pharmacokinetic profiles). Voriconazole plasma measured using HPLC. Non-compartmental analysis performed WinNonlin. Population models developed NONMEM. Covariate built forward addition reverse removal approach. Precision parameter estimation evaluated by bootstrapping. Adequate regimens Monte Carlo simulations.There good correlation between AUCo-∞ trough concentrations. Bioavailability is substantially reduced BMT during early post-transplant period. Pharmacokinetics significantly postoperative time, liver function CYP2C19 genotype patients. time cystic fibrosis Patients (CF) exhibited lower bioavailability than non-CF Donor characteristics had no significant similar Compared higher clearance volume distribution.In conclusion, weight-adjusted or resulted highly variable transplant, Given that concentration measure drug (AUC), dose can be individualized based on demonstrated inadequacy oral administration adequacy intravenous first few post-operative days, followed doses optimal exposure.