CYP2D6 isoenzyme and ABCB1 gene polymorphisms associated with postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy: a randomized trial

Angela Henrique Silva Ribeiro; Estêvão Luiz Carvalho Braga; Nathalia de Araújo Gouveia Ferreira; Beni Olej; Nubia Verçosa; Leonardo dos Santos Antunes; Ismar Lima Cavalcanti

doi:10.1016/j.bjane.2023.02.002

Original Investigation

CYP2D6 isoenzyme and ABCB1 gene polymorphisms associated with postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy: a randomized trial

Angela Henrique Silva Ribeiro, Estêvão Luiz Carvalho Braga, Nathalia de Araújo Gouveia Ferreira, Beni Olej, Nubia Verçosa, Leonardo dos Santos Antunes, Ismar Lima Cavalcanti

http://dx.doi.org/10.1016/j.bjane.2023.02.002 Braz J Anesthesiol, Ahead of Print, 2023

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Abstract

Introduction

Postoperative nausea and vomiting is still a common complication. Serotonin receptor antagonists are commonly used in clinical practice for antiemetic prophylaxis. Interindividual variations in drug response, including single nucleotide polymorphisms, are related to pharmacokinetic and pharmacodynamic changes in these drugs and may lead to a poor therapeutic response. This study aimed to evaluate the influence of CYP2D6 isoenzyme and ABCB1 gene polymorphisms on the frequency of postoperative nausea and vomiting with the use of ondansetron or palonosetron.

Methods

A randomized, double-blind clinical trial including 82 women aged 60 years or over undergoing laparoscopic cholecystectomy was conducted. Patients were randomized to receive either ondansetron or palonosetron for postoperative nausea and vomiting prophylaxis. DNA was extracted from saliva. Genetic polymorphisms were analyzed by real-time polymerase chain reaction. The following polymorphisms were analyzed: rs3892097 C/T, rs1128503 A/G, rs16947 A/G, rs1065852 A/G, rs1045642 A/G, rs2032582 C/A, and rs20325821 C/A.

Results

Overall, vomiting, and severe nausea occurred in 22.5% and 57.5% of patients, respectively. In the palonosetron group, patients with the GG genotype (rs16947 A/G) experienced more severe nausea (p = 0.043). In the ondansetron group, patients with the AA genotype (rs16947 A/G) presented mild nausea (p = 0.034), and those with the AA genotype (rs1065852 A/G) experienced more vomiting (p = 0.034).

Conclusion

A low antiemetic response was observed with ondansetron in the presence of the AA genotype (rs16947 A/G) and the AA genotype (rs1065852 A/G), and a low therapeutic response was found with palonosetron in the presence of the GG genotype (rs16947 A/G) in laparoscopic cholecystectomy.

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ClinicalTrials.gov.

Keywords

Antiemetics, Genetic polymorphism, Laparoscopic cholecystectomy, Ondansetron, Palonosetron, Postoperative nausea and vomiting

References

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The impact of current antiemetic practices on patient outcomes: a prospective study on high-risk patients

Anesth Analg, 107 (2) (2008), pp. 452-458
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T Gan, F Sloan, L Dear Gde, HE El-Moalem, DA Lubarsky

How much are patients willing to pay to avoid postoperative nausea and vomiting?

Anesth Analg, 92 (2) (2001), pp. 393-400
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S Chatterjee, A Rudra, S. Sengupta

Current concepts in the management of postoperative nausea and vomiting

Anesthesiol Res Pract, 2011 (2011), Article 748031
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I Bala, N Bharti, S Murugesan, R. Gupta

Comparison of palonosetron with palonosetron-dexamethasone combination for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy

Minerva Anestesiol, 80 (7) (2014), pp. 779-784
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CC Apfel, N. Roewer

Risk assessment of postoperative nausea and vomiting

Int Anesthesiol Clin, 41 (4) (2003), pp. 13-32
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TJ Gan, P Diemunsch, AS Habib, A Kovac, P Kranke, TA Meyer, et al.

Consensus guidelines for the management of postoperative nausea and vomiting

Anesth Analg, 118 (1) (2014), pp. 85-113
7

CC Apfel, K Korttila, M Abdalla, H Kerger, A Turan, I Vedder, et al.

A factorial trial of six interventions for the prevention of postoperative nausea and vomiting

N Engl J Med, 350 (24) (2004), pp. 2441-2451
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[cited 2022 Feb 5]. Available from:

https://gntech.med.br/
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P. Nagele

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Best Pract Res Clin Anaesthesiol, 25 (4) (2011), pp. 549-555
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KP Singh, AA Dhruva, E Flowers, KM Kober, C. Miaskowski

A review of the literature on the relationships between genetic polymorphisms and chemotherapy-induced nausea and vomiting

Crit Rev Oncol Hematol, 121 (2018), pp. 51-61
11

KA Phillips, DL Veenstra, E Oren, JK Lee, W Sadee

Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review

JAMA, 286 (18) (2001), pp. 2270-2279
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P Borst, AH. Schinkel

P-glycoprotein ABCB1: a major player in drug handling by mammals

J Clin Invest, 123 (10) (2013), pp. 4131-4133
13

MO Babaoglu, B Bayar, AS Aynacioglu, R Kerb, H Abali, I Celik, et al.

Association of the ABCB1 3435C>T polymorphism with antiemetic efficacy of 5-hydroxytryptamine type 3 antagonists

Clin Pharmacol Ther, 78 (6) (2005), pp. 619-626
14

KY Ho, TJ. Gan

Pharmacology, pharmacogenetics, and clinical efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting

Curr Opin Anaesthesiol, 19 (6) (2006), pp. 606-611
15

S Klenke, UH. Frey

Genetic variability in postoperative nausea and vomiting: A systematic review

Eur J Anaesthesiol, 37 (11) (2020), pp. 959-968
16

P Lopez-Morales, D Flores-Funes, EG Sanchez-Migallon, RJ Liron-Ruiz, JL. Aguayo-Albasini

Genetic factors associated with postoperative nausea and vomiting: a systematic review

J Gastrointest Surg, 22 (9) (2018), pp. 1645-1651
17

DA Perwitasari, JA Wessels, RJ van der Straaten, RF Baak-Pablo, M Mustofa, M Hakimi, et al.

Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy

Jpn J Clin Oncol, 41 (10) (2011), pp. 1168-1176
18

EL Carvalho Braga, NV Figueiredo, L Barrucand, IL. Cavalcanti

Use of palonosetron and ondansetron in the prophylaxis of postoperative nausea and vomiting in women 60 years of age or older undergoing laparoscopic cholecystectomy: A randomised double-blind study

Eur J Anaesthesiol, 36 (3) (2019), pp. 241-242
19

B Laha, A Hazra, S. Mallick

Evaluation of antiemetic effect of intravenous palonosetron versus intravenous ondansetron in laparoscopic cholecystectomy: a randomized controlled trial

Indian J Pharmacol, 45 (1) (2013), pp. 24-29
20

MS Kim, JR Lee, EM Choi, EH Kim, SH. Choi

Association of 5-HT3B receptor gene polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting

Yonsei Med J, 56 (5) (2015), pp. 1415-1420
21

JW Song, JK Shim, SH Choi, S Soh, J Jang, YL. Kwak

Comparison of ramosetron and palonosetron for preventing nausea and vomiting after spinal surgery: association with ABCB1 polymorphisms

J Neurosurg Anesthesiol, 29 (4) (2017), pp. 406-414
22

EM Choi, MG Lee, SH Lee, KW Choi, SH. Choi

Association of ABCB1 polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting

Anaesthesia, 65 (10) (2010), pp. 996-1000
23

H He, JY Yin, YJ Xu, X Li, Y Zhang, ZG Liu, et al.

Association of ABCB1 polymorphisms with the efficacy of ondansetron in chemotherapy-induced nausea and vomiting

Clin Ther, 36 (8) (2014), pp. 1242-1252

e2
24

TJ. Gan

Risk factors for postoperative nausea and vomiting

Anesth Analg, 102 (6) (2006), pp. 1884-1898
25

UM Stamer, M Schmutz, T Wen, V Banz, C Lippuner, L Zhang, et al.

A serotonin transporter polymorphism is associated with postoperative nausea and vomiting: An observational study in two different patient cohorts

Eur J Anaesthesiol, 36 (8) (2019), pp. 566-574
26

Y Mitsunaga, T Kubota, A Ishiguro, Y Yamada, H Sasaki, K Chiba, et al.

Frequent occurrence of CYP2D6*10 duplication allele in a Japanese population

Mutat Res, 505 (1-2) (2002), pp. 83-85
27

S Klenke, GJ de Vries, L Schiefer, N Seyffert, HS Bachmann, J Peters, et al.

CHRM3 rs2165870 polymorphism is independently associated with postoperative nausea and vomiting, but combined prophylaxis is effective

Br J Anaesth, 121 (1) (2018), pp. 58-65
28

SC Sim, M. Ingelman-Sundberg

Update on allele nomenclature for human cytochromes P450 and the Human Cytochrome P450 Allele (CYP-allele) nomenclature database

Methods Mol Biol, 987 (2013), pp. 251-259
29

ELC Braga, N Vercosa, IL. Cavalcanti

Comparative study between fosaprepitant and palonosetron in the prophylaxis of postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy: prospective, randomized and double-blind study

Front Pharmacol, 13 (2022), Article 915347
30

PK Janicki, R Vealey, J Liu, J Escajeda, M Postula, K. Welker

Genome-wide Association study using pooled DNA to identify candidate markers mediating susceptibility to postoperative nausea and vomiting

Anesthesiology, 115 (1) (2011), pp. 54-64

[1] 1

PF White, JF O'Hara, CR Roberson, RH Wender, KA Candiotti, P-OS. Group

The impact of current antiemetic practices on patient outcomes: a prospective study on high-risk patients

Anesth Analg, 107 (2) (2008), pp. 452-458

[2] 2

T Gan, F Sloan, L Dear Gde, HE El-Moalem, DA Lubarsky

How much are patients willing to pay to avoid postoperative nausea and vomiting?

Anesth Analg, 92 (2) (2001), pp. 393-400

[3] 3

S Chatterjee, A Rudra, S. Sengupta

Current concepts in the management of postoperative nausea and vomiting

Anesthesiol Res Pract, 2011 (2011), Article 748031

[4] 4

I Bala, N Bharti, S Murugesan, R. Gupta

Comparison of palonosetron with palonosetron-dexamethasone combination for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy

Minerva Anestesiol, 80 (7) (2014), pp. 779-784

[5] 5

CC Apfel, N. Roewer

Risk assessment of postoperative nausea and vomiting

Int Anesthesiol Clin, 41 (4) (2003), pp. 13-32

[6] 6

TJ Gan, P Diemunsch, AS Habib, A Kovac, P Kranke, TA Meyer, et al.

Consensus guidelines for the management of postoperative nausea and vomiting

Anesth Analg, 118 (1) (2014), pp. 85-113

[7] 7

CC Apfel, K Korttila, M Abdalla, H Kerger, A Turan, I Vedder, et al.

A factorial trial of six interventions for the prevention of postoperative nausea and vomiting

N Engl J Med, 350 (24) (2004), pp. 2441-2451

[8] 8

Gntech [Internet]

(2022)

[cited 2022 Feb 5]. Available from:

https://gntech.med.br/

[9] 9

P. Nagele

Perioperative genomics

Best Pract Res Clin Anaesthesiol, 25 (4) (2011), pp. 549-555

[10] 10

KP Singh, AA Dhruva, E Flowers, KM Kober, C. Miaskowski

A review of the literature on the relationships between genetic polymorphisms and chemotherapy-induced nausea and vomiting

Crit Rev Oncol Hematol, 121 (2018), pp. 51-61

[11] 11

KA Phillips, DL Veenstra, E Oren, JK Lee, W Sadee

Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review

JAMA, 286 (18) (2001), pp. 2270-2279

[12] 12

P Borst, AH. Schinkel

P-glycoprotein ABCB1: a major player in drug handling by mammals

J Clin Invest, 123 (10) (2013), pp. 4131-4133

[13] 13

MO Babaoglu, B Bayar, AS Aynacioglu, R Kerb, H Abali, I Celik, et al.

Association of the ABCB1 3435C>T polymorphism with antiemetic efficacy of 5-hydroxytryptamine type 3 antagonists

Clin Pharmacol Ther, 78 (6) (2005), pp. 619-626

[14] 14

KY Ho, TJ. Gan

Pharmacology, pharmacogenetics, and clinical efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting

Curr Opin Anaesthesiol, 19 (6) (2006), pp. 606-611

[15] 15

S Klenke, UH. Frey

Genetic variability in postoperative nausea and vomiting: A systematic review

Eur J Anaesthesiol, 37 (11) (2020), pp. 959-968

[16] 16

P Lopez-Morales, D Flores-Funes, EG Sanchez-Migallon, RJ Liron-Ruiz, JL. Aguayo-Albasini

Genetic factors associated with postoperative nausea and vomiting: a systematic review

J Gastrointest Surg, 22 (9) (2018), pp. 1645-1651

[17] 17

DA Perwitasari, JA Wessels, RJ van der Straaten, RF Baak-Pablo, M Mustofa, M Hakimi, et al.

Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy

Jpn J Clin Oncol, 41 (10) (2011), pp. 1168-1176

[18] 18

EL Carvalho Braga, NV Figueiredo, L Barrucand, IL. Cavalcanti

Use of palonosetron and ondansetron in the prophylaxis of postoperative nausea and vomiting in women 60 years of age or older undergoing laparoscopic cholecystectomy: A randomised double-blind study

Eur J Anaesthesiol, 36 (3) (2019), pp. 241-242

[19] 19

B Laha, A Hazra, S. Mallick

Evaluation of antiemetic effect of intravenous palonosetron versus intravenous ondansetron in laparoscopic cholecystectomy: a randomized controlled trial

Indian J Pharmacol, 45 (1) (2013), pp. 24-29

[20] 20

MS Kim, JR Lee, EM Choi, EH Kim, SH. Choi

Association of 5-HT3B receptor gene polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting

Yonsei Med J, 56 (5) (2015), pp. 1415-1420

[21] 21

JW Song, JK Shim, SH Choi, S Soh, J Jang, YL. Kwak

Comparison of ramosetron and palonosetron for preventing nausea and vomiting after spinal surgery: association with ABCB1 polymorphisms

J Neurosurg Anesthesiol, 29 (4) (2017), pp. 406-414

[22] 22

EM Choi, MG Lee, SH Lee, KW Choi, SH. Choi

Association of ABCB1 polymorphisms with the efficacy of ondansetron for postoperative nausea and vomiting

Anaesthesia, 65 (10) (2010), pp. 996-1000

[23] 23

H He, JY Yin, YJ Xu, X Li, Y Zhang, ZG Liu, et al.

Association of ABCB1 polymorphisms with the efficacy of ondansetron in chemotherapy-induced nausea and vomiting

Clin Ther, 36 (8) (2014), pp. 1242-1252

e2

[24] 24

TJ. Gan

Risk factors for postoperative nausea and vomiting

Anesth Analg, 102 (6) (2006), pp. 1884-1898

[25] 25

UM Stamer, M Schmutz, T Wen, V Banz, C Lippuner, L Zhang, et al.

A serotonin transporter polymorphism is associated with postoperative nausea and vomiting: An observational study in two different patient cohorts

Eur J Anaesthesiol, 36 (8) (2019), pp. 566-574

[26] 26

Y Mitsunaga, T Kubota, A Ishiguro, Y Yamada, H Sasaki, K Chiba, et al.

Frequent occurrence of CYP2D6*10 duplication allele in a Japanese population

Mutat Res, 505 (1-2) (2002), pp. 83-85

[27] 27

S Klenke, GJ de Vries, L Schiefer, N Seyffert, HS Bachmann, J Peters, et al.

CHRM3 rs2165870 polymorphism is independently associated with postoperative nausea and vomiting, but combined prophylaxis is effective

Br J Anaesth, 121 (1) (2018), pp. 58-65

[28] 28

SC Sim, M. Ingelman-Sundberg

Update on allele nomenclature for human cytochromes P450 and the Human Cytochrome P450 Allele (CYP-allele) nomenclature database

Methods Mol Biol, 987 (2013), pp. 251-259

[29] 29

ELC Braga, N Vercosa, IL. Cavalcanti

Comparative study between fosaprepitant and palonosetron in the prophylaxis of postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy: prospective, randomized and double-blind study

Front Pharmacol, 13 (2022), Article 915347

[30] 30

PK Janicki, R Vealey, J Liu, J Escajeda, M Postula, K. Welker

Genome-wide Association study using pooled DNA to identify candidate markers mediating susceptibility to postoperative nausea and vomiting

Anesthesiology, 115 (1) (2011), pp. 54-64

CYP2D6 isoenzyme and ABCB1 gene polymorphisms associated with postoperative nausea and vomiting in women undergoing laparoscopic cholecystectomy: a randomized trial

Angela Henrique Silva Ribeiro, Estêvão Luiz Carvalho Braga, Nathalia de Araújo Gouveia Ferreira, Beni Olej, Nubia Verçosa, Leonardo dos Santos Antunes, Ismar Lima Cavalcanti

Abstract

Introduction

Methods

Results

Conclusion

Register

Keywords

References

Links

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