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• W2247156784 abstract "Introduction: Phenytoin (PTN) is a highly protein bound anticonvulsant agent commonly employed in intensive care. Given the high morbidity associated with uncontrolled seizures in this setting, rapid attainment of therapeutic concentrations is mandated.Objectives: To define the population pharmacokinetics (PK) of phenytoin in the critically ill, in addition to risk factors for sub-therapeutic dosing.Methods: Free and total PTN concentrations were measured in serum by means of high performance liquid chromatography following microfiltration, two to three times in the first 24 h after a loading dose. Population PK modelling, including intra and interindividual variability, were determined using NONMEM(R). Results: Fifty three patients (total of 153 plasma samples) where included in the study. Demographic and pharmacokinetic data are presented in table 1. A one compartment linear model adequately described the pharmacokinetics of loading doses of PTN. The mean clearance and volume of distribution for PTN were 0.024 L kg/h and 1.08 L/kg respectively. The loading dose was within recommended guidelines (10–20 mg/kg) for the majority of cases. Protein binding was consistently ~ 90% when albumin levels were[25 mmol/L and hypoalbuminaemia was associated with higher unbound (free) PTN levels. The percentage of free and total trough levels that were therapeutic were 49% and 38% respectively. Conclusions: This study has developed a population PK model of PTN loading in critically ill patients. Hypoalbuminaemia was shown to be a critical factor in dosing requirements. In approximately 50% of patients, the trough PTN level was below the therapeutic range, suggesting that higher dosing may be required.© Springer" @default.
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• W2247156784 date "2010-01-01" @default.
• W2247156784 modified "2023-09-27" @default.
• W2247156784 title "Assessment of adequacy of loading dose of phenytoin (PTN) in adult intensive care patients using population pharmacokinetics" @default.
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