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  • Effects of cytochrome P450 (CYP)2C19 polymorphisms on pharmacokinetics of phenobarbital in neonates and infants with seizures

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Drug therapy
Original articles
Effects of cytochrome P450 (CYP)2C19 polymorphisms on pharmacokinetics of phenobarbital in neonates and infants with seizures
  1. Soon Min Lee1,
  2. Jae Yong Chung2,3,
  3. Young Mock Lee1,
  4. Min Soo Park1,3,
  5. Ran Namgung1,
  6. Kook In Park1,
  7. Chul Lee1
  1. 1Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
  2. 2Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea
  3. 3Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea
  1. Correspondence to M S Park, Department of Pediatrics and Clinical Pharmacology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea; minspark{at}yuhs.ac

Abstract

Background Phenobarbital (PB), commonly used as the preferred treatment for neonatal seizure, is a drug that requires careful dose adjustments based on therapeutic drug monitoring. It has been reported that PB metabolism was affected by cytochrome P450 (CYP)2C19 polymorphisms in adults requiring dose adjustment.

Aim This study aimed to evaluate the effects of CYP2C19 genetic polymorphisms on PB pharmacokinetics (PK) in neonates and infants with seizures.

Methods CYP2C19 (wild type: CYP2C19*1/*1, heterozygous extensive metabolisers: CYP2C19*1/*2, *1/*3 and poor metabolisers: CYP2C19*2/*2, *2/*3) genetic polymorphisms in 52 neonates and infants with seizures were analysed. PK parameters were compared based on genotypes. The NONMEM program was used for population PK modelling.

Results No significant difference in PB clearance (CL), volume of distribution (Vd) and concentrations were shown among the CYP2C19 genotype groups. The results of PK modelling were as follows: Vd=3590 ×(body weight (BWT)/4)0.766 ×(AGE/2)0.283 and CL=32.6×(BWT/4)1.21.

Conclusions PB PK parameters of neonates and infants with seizures were not significantly different among the groups with different CYP2C19 genotypes. The addition of CYP2C19 genotyping to PK models did not improve the dosing strategies in neonates and infants.

https://doi.org/10.1136/archdischild-2011-300538

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    Footnotes

    • Funding This work was funded by a faculty research grant from Yonsei University College of Medicine.

    • Competing interests None.

    • Ethics approval Yonsei University IRB no. 4-2008-0029.

    • Patient consent Obtained.

    • Provenance and peer review Not commissioned; externally peer reviewed.