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Eur J Drug Metab Pharmacokinet. 2016 Oct;41(5):511-5. doi: 10.1007/s13318-015-0289-y.

Impact of the Cytochrome P450 2B6 (CYP2B6) Gene Polymorphism c.516G>T (rs3745274) on Propofol Dose Variability.

Author information

  • 1Graduate Program in Biological Sciences and Rehabilitation, Methodist University Centre, IPA, Porto Alegre, RS, Brazil.
  • 2Graduate Program in Biological Sciences and Rehabilitation, Methodist University Centre, IPA, Porto Alegre, RS, Brazil. mariluf@ufcspa.edu.br.
  • 3Department of Basic Health Sciences, Federal Health Sciences University of Porto Alegre, Rua Sarmento Leite, 245/403, CEP 90050-170, Porto Alegre, RS, Brazil. mariluf@ufcspa.edu.br.

Abstract

BACKGROUND AND OBJECTIVES:

Propofol is the most commonly used hypnotic worldwide, but its effective dose varies greatly between individuals. The present study sought to investigate the relationship between the c.516G>T polymorphism in the CYP2B6 (cytochrome P450 2B6) gene and the required propofol dose.

METHODS:

One hundred and eight patients treated with propofol were recruited, and environmental, clinical and surgical data were collected. Genotyping for the c.516G>T polymorphism was performed by real-time PCR. Multiple linear regression analysis was performed to estimate the predictive variables of the total propofol dose.

RESULTS:

For patients under general anaesthesia, the predictive variables of the total propofol dose were surgery duration (partial R (2) = 19.9 %), age (partial R (2) = 10.5 %), weight (partial R (2) = 10.1 %) and presence of the T allele (partial R (2) = 6.8 %). From the estimated coefficient of regression values, the surgery duration and weight were the factors that increased the propofol dose, while age and presence of the T allele decreased the total dose of the drug needed. The total propofol doses based on the GG or GT/TT genotypes were 151.5 ± 64.2 mg and 129.3 ± 44.6 mg, respectively (p = 0.043).

CONCLUSIONS:

Our results indicate that 34 % of the variance in the required propofol dose may be explained by these factors and that CYP2B6 c.516G>T polymorphism, which decreases the metabolism of the drug, accounts for approximately 7 % of the drug dosage. Our results show the possible influence of CYP2B6 c.516G>T genetic variant on propofol dose in patients under general anaesthesia.

PMID:
26141406
DOI:
10.1007/s13318-015-0289-y
[PubMed - in process]
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