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Population pharmacokinetics of theophylline in premature Korean infants
- Source :
- Therapeutic drug monitoring. 35(3)
- Publication Year :
- 2013
-
Abstract
- The aim of this study was to investigate the population pharmacokinetics of theophylline in premature Korean infants and to assess the influence of clinical covariates.Blood samples were first obtained after 1 week of maintenance dosing and then acquired approximately 4 weeks after continuous dosing. The time points were just before dosing and 2, 4, or 6 hours (at randomly assigned time points) after dosing. Two single-nucleotide polymorphism markers, -3860 GA (CYP1A2*1C) and -163CA (CYP1A2*1F), were genotyped. Gestational age (GA), postnatal age (PNA), postconceptional age (PCA = GA + PNA), body weight (BW), height, serum AST, serum ALT, serum BUN, serum creatinine, oxygen support, sex, delivery mode, and CYP1A2 genotypes were used for covariate model building. External validation was analyzed using data from an additional 27 patients.A total of 334 serum concentration measurements were made in 100 patients. A one-compartment absorptive model with first-order elimination was fitted to the data in NONMEM (version 7.1.2). The final model included the following parameters: Clearance (L/h) = 0.00492 × (BW)(3.53) + 0.00646 × (PNA), and volume of distribution (L) = 1.53 × (BW). The addition of the CYP1A2*1C or CYP1A2*1F genotypes to the model did not improve the model. The external validation results confirmed the predictive performance without bias in the final model.The selected covariates were generally consistent with previous studies. However, the mean volume of distribution was higher than the values reported in other population pharmacokinetic studies, which may have been due to the use of 2 sampling time points. The predictive performance was reasonably acceptable. Therefore, the present model may permit more accurate selection of doses to achieve target theophylline concentrations in premature infants.
- Subjects :
- Male
Pediatrics
medicine.medical_specialty
Time Factors
Genotype
Population pharmacokinetics
Models, Biological
Polymorphism, Single Nucleotide
Asian People
Theophylline
Cytochrome P-450 CYP1A2
Republic of Korea
Medicine
Humans
Pharmacology (medical)
Tissue Distribution
Dosing
Prospective Studies
Prospective cohort study
Retrospective Studies
Pharmacology
medicine.diagnostic_test
business.industry
Infant, Newborn
Retrospective cohort study
Bronchodilator Agents
Clinical trial
Multicenter study
Nonlinear Dynamics
Therapeutic drug monitoring
Female
business
Infant, Premature
medicine.drug
Subjects
Details
- ISSN :
- 15363694
- Volume :
- 35
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Therapeutic drug monitoring
- Accession number :
- edsair.doi.dedup.....60baee5de87d84116a667c228c6e58b2