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Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Research Article

Effects of CYP2B6 Genetic Variants on the Propofol Dose and Response among Jordanian Arabic Patients Undergoing General Anesthesia

Author(s): Mustafa Alrabayah, Islam Mohammad Massad, Amer Imraish, Yazun Jarrar, Faysal Massad, Hasan Guzu, Basil Abufares, Afnan Al-Oran, Malik Mohammad Alkharabsheh, Nour Haroon, Mohammad Asa'ad Ismail, Bara'a Qaqish and Malik Zihlif*

Volume 23, Issue 14, 2022

Published on: 07 February, 2023

Page: [1156 - 1161] Pages: 6

DOI: 10.2174/1389200224666230130110350

Price: $65

Abstract

Background: Propofol is the most commonly used general anesthetic drug in many countries, including Jordan. However, there is a wide variation in the propofols' dose and response among the patients. Genetic variation in the cytochrome (CYP) 2B6 gene affects propofol metabolism and might affect propofol dose and response.

Aims: This study aimed to determine the influence of major genetic alleles of the CYP2B6 gene, CYP2B6*2A, *6A, *3, *4A, and *5A, on the required propofol dose and response among Jordanian Arabic patients attending The University of Jordan Hospital.

Methods: A total of 155 patients were administrated propofol. The propofol response was evaluated by monitoring the time to reach the bispectral index of 60 (BIS60) for every patient. The CYP2B6 genetic variants were genotyped by polymerase chain reaction followed by restriction through specific enzymes for CYP2B6 variants.

Results: It is found that patients with variant CYP2B6*2A and *4A alleles required significantly (P < 0.05) lower propofol doses, while patients with variant CYP2B6*6A, *3, and *5A alleles required higher propofol doses in comparison with patients carrying the wild CYP2B6 alleles. Patients with variant CYP2B6*2A and *3 alleles needed a significantly (P < 0.05) shorter while patients with variant CYP2B6*5A allele needed longer time of BIS60 than patients with wild CYP2B6*2A, *3, and *5A alleles.

Conclusion: It is concluded that CYP2B6 genetic variants affect propofol dose and can explain, at least partly, the inter-individual variation in the propofol response. Further clinical studies with a larger sample size are needed to confirm the findings of this study.

Graphical Abstract

[1]
Chidambaran, V.; Costandi, A.; D’Mello, A. Propofol: A review of its role in pediatric anesthesia and sedation. CNS Drugs, 2015, 29(7), 543-563.
[http://dx.doi.org/10.1007/s40263-015-0259-6] [PMID: 26290263]
[2]
Dinis-Oliveira, R.J. Metabolic profiles of propofol and fospropofol: Clinical and forensic interpretative aspects. BioMed Res. Int., 2018, 2018, 1-16.
[http://dx.doi.org/10.1155/2018/6852857] [PMID: 29992157]
[3]
Jarrar, Y.B.; Lee, S.J. Molecular functionality of CYP2C9 polymorphisms and their influence on drug therapy. Drug Metabol. Drug Interact., 2014, 29(4), 211-220.
[http://dx.doi.org/10.1515/dmdi-2014-0001] [PMID: 24825094]
[4]
Jarrar, Y.B.; Cha, E.Y.; Seo, K.A.; Ghim, J.L.; Kim, H.J.; Kim, D.H.; Lee, S.J.; Shin, J.G. Determination of major UDP-glucuronosyltransferase enzymes and their genotypes responsible for 20-HETE glucuronidation. J. Lipid Res., 2014, 55(11), 2334-2342.
[http://dx.doi.org/10.1194/jlr.M051169] [PMID: 25249502]
[5]
Allegaert, K.; Peeters, M.Y.; Verbesselt, R.; Tibboel, D.; Naulaers, G.; de Hoon, J.N.; Knibbe, C.A. Inter-individual variability in propofol pharmacokinetics in preterm and term neonates. Br. J. Anaesth., 2007, 99(6), 864-870.
[http://dx.doi.org/10.1093/bja/aem294] [PMID: 17965417]
[6]
Khan, M.S.; Zetterlund, E.L.; Gréen, H.; Oscarsson, A.; Zackrisson, A.L.; Svanborg, E.; Lindholm, M.L.; Persson, H.; Eintrei, C. Pharmacogenetics, plasma concentrations, clinical signs and EEG during propofol treatment. Basic Clin. Pharmacol. Toxicol., 2014, 115(6), 565-570.
[http://dx.doi.org/10.1111/bcpt.12277] [PMID: 24891132]
[7]
Mourão, A.L.; de Abreu, F.G.; Fiegenbaum, M. Impact of the cytochrome P450 2B6 (CYP2B6) gene polymorphism c.516G>T (rs3745274) on propofol dose variability. Eur. J. Drug Metab. Pharmacokinet., 2016, 41(5), 511-515.
[http://dx.doi.org/10.1007/s13318-015-0289-y] [PMID: 26141406]
[8]
Iohom, G.; Ni Chonghaile, M.; OʼBrien, J.K.; Cunningham, A.J.; Fitzgerald, D.F.; Shields, D.C. An investigation of potential genetic determinants of propofol requirements and recovery from anaesthesia. Eur. J. Anaesthesiol., 2007, 24(11), 912-919.
[http://dx.doi.org/10.1017/S0265021507000476] [PMID: 17555608]
[9]
Daabiss, M. American society of anaesthesiologists physical status classification. Indian J. Anaesth., 2011, 55(2), 111-115.
[http://dx.doi.org/10.4103/0019-5049.79879] [PMID: 21712864]
[10]
Rüsch, D.; Arndt, C.; Eberhart, L.; Tappert, S.; Nageldick, D.; Wulf, H. Bispectral index to guide induction of anesthesia: A randomized controlled study. BMC Anesthesiol., 2018, 18(1), 66.
[http://dx.doi.org/10.1186/s12871-018-0522-8] [PMID: 29902969]
[11]
Lang, T.; Klein, K.; Fischer, J.; Nüssler, A.; Neuhaus, P.; Hofmann, U.; Eichelbaum, M.; Schwab, M.; Zanger, U. Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics, 2001, 11(5), 399-415.
[http://dx.doi.org/10.1097/00008571-200107000-00004] [PMID: 11470993]
[12]
Kaskinoro, K.; Maksimow, A.; Långsjö, J.; Aantaa, R.; Jääskeläinen, S.; Kaisti, K.; Särkelä, M.; Scheinin, H. Wide inter-individual variability of bispectral index and spectral entropy at loss of consciousness during increasing concentrations of dexmedetomidine, propofol, and sevoflurane. Br. J. Anaesth., 2011, 107(4), 573-580.
[http://dx.doi.org/10.1093/bja/aer196] [PMID: 21733891]
[13]
Pavlovic, D.; Budic, I.; Jevtovic Stoimenov, T.; Stokanovic, D.; Marjanovic, V.; Stevic, M.; Slavkovic, M.; Simic, D. The effect of UGT1A9, CYP2B6 and CYP2C9 genes polymorphism on propofol pharmacokinetics in children. Pharm. Genomics Pers. Med., 2020, 13, 13-27.
[http://dx.doi.org/10.2147/PGPM.S231329] [PMID: 32021384]
[14]
Mikstacki, A.; Zakerska-Banaszak, O.; Skrzypczak-Zielinska, M.; Tamowicz, B.; Prendecki, M.; Dorszewska, J.; Molinska-Glura, M.; Waszak, M.; Slomski, R. The effect of UGT1A9, CYP2B6 and CYP2C9 genes polymorphism on individual differences in propofol pharmacokinetics among polish patients undergoing general anaesthesia. J. Appl. Genet., 2017, 58(2), 213-220.
[http://dx.doi.org/10.1007/s13353-016-0373-2] [PMID: 27826892]
[15]
Wang, Y.B.; Zhang, R.Z.; Huang, S.H.; Wang, S.B.; Xie, J.Q. Relationship between UGT1A9 gene polymorphisms, efficacy, and safety of propofol in induced abortions amongst Chinese population: A population-based study. Biosci. Rep., 2017, 37(5), BSR20170722.
[http://dx.doi.org/10.1042/BSR20170722] [PMID: 28899924]
[16]
Rotger, M.; Tegude, H.; Colombo, S.; Cavassini, M.; Furrer, H.; Décosterd, L.; Blievernicht, J.; Saussele, T.; Günthard, H.F.; Schwab, M.; Eichelbaum, M.; Telenti, A.; Zanger, U.M. Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals. Clin. Pharmacol. Ther., 2007, 81(4), 557-566.
[http://dx.doi.org/10.1038/sj.clpt.6100072] [PMID: 17235330]
[17]
Hofmann, M.H.; Blievernicht, J.K.; Klein, K.; Saussele, T.; Schaeffeler, E.; Schwab, M.; Zanger, U.M. Aberrant splicing caused by single nucleotide polymorphism c.516G>T [Q172H], a marker of CYP2B6*6, is responsible for decreased expression and activity of CYP2B6 in liver. J. Pharmacol. Exp. Ther., 2008, 325(1), 284-292.
[http://dx.doi.org/10.1124/jpet.107.133306] [PMID: 18171905]
[18]
Mangó, K.; Kiss, Á.F.; Fekete, F.; Erdős, R.; Monostory, K. CYP2B6 allelic variants and non-genetic factors influence CYP2B6 enzyme function. Sci. Rep., 2022, 12(1), 2984.
[http://dx.doi.org/10.1038/s41598-022-07022-9] [PMID: 35194103]
[19]
Auton, A.; Abecasis, G.R.; Altshuler, D.M.; Durbin, R.M.; Abecasis, G.R.; Bentley, D.R. 1000 Genomes Project Consortium. A global reference for human genetic variation. Nature, 2015, 526(7571), 68-74.
[http://dx.doi.org/10.1038/nature15393] [PMID: 26432245]

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