Application of routine monitoring data for determination of the population pharmacokinetics and enteral bioavailability of phenytoin in neonates and infants with seizures

Mohammed Al Za'abi, Anders Lanner, Xiao Xiaonian, Timothy Donovan, Bruce Charles*

*المؤلف المقابل لهذا العمل

نتاج البحث: المساهمة في مجلةArticleمراجعة النظراء

16 اقتباسات (Scopus)

ملخص

This study investigated the population pharmacokinetics and the enteral bioavailability of phenytoin (PTN) in neonates and infants with seizures. Data from 83 patients were obtained retrospectively from medical records. A 1-compartment model was fitted to the log-transformed concentration data using NONMEM. Between-subject variability and interoccasion variability were modelled exponentially together with a log transform, both-sides exponential residual unexplained variance model. Covariates in nested models were screened for significance. Model robustness was assessed by bootstrapping with replacement (n = 500) from the study data. The parameters of the final pharmacokinetic model were clearance (L/h) = 0.826·[weight (WT, kg) ÷ 70]·[1 + 0.0692·(postnatal age (d) - 11)]; volume of distribution (L) = 74.2·[WT (kg) ÷ 70]; absolute enteral bioavailability = 0.76; absorption rate constant (h) = 0.167. The between-subject variability for clearance and volume of distribution was 74.2% and 65.6%, respectively. The interoccasion variability for clearance was 54.4%. The unexplained variability was 51.1%. Final model parameter values deviated from median bootstrap estimates by less than 9%. Phenytoin disposition in neonates and infants can be described satisfactorily by linear pharmacokinetics. The values of allometrically scaled clearance and volume were similar to adult values, suggesting no major kinetic differences between adults and infants on the basis of size alone. Postnatal age independently influenced clearance. Switching from enteral to intravenous routes may require a dosage adjustment. The results of this study provide a basis for more rational prescribing of phenytoin in infants and neonates.

اللغة الأصليةEnglish
الصفحات (من إلى)793-799
عدد الصفحات7
دوريةTherapeutic Drug Monitoring
مستوى الصوت28
رقم الإصدار6
المعرِّفات الرقمية للأشياء
حالة النشرPublished - ديسمبر 2006
منشور خارجيًانعم

ASJC Scopus subject areas

  • ???subjectarea.asjc.3000.3004???
  • ???subjectarea.asjc.2700.2736???

بصمة

أدرس بدقة موضوعات البحث “Application of routine monitoring data for determination of the population pharmacokinetics and enteral bioavailability of phenytoin in neonates and infants with seizures'. فهما يشكلان معًا بصمة فريدة.

قم بذكر هذا