Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 11, November, p. 1499–1503

doi: 10.17219/acem/69451

Publication type: original article

Language: English

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CYP2D6 basic genotyping as a potential tool to improve the antiemetic efficacy of ondansetron in prophylaxis of postoperative nausea and vomiting

Przemysław A. Niewiński1,A,D, Robert Wojciechowski2,B, Marek Śliwiński2,B, Magdalena E. Hurkacz1,B,C,F, Krystyna Głowacka1,B, Krystyna Orzechowska-Juzwenko1,A,E, Anna K. Wiela-Hojeńska1,A,E,F

1 Department of Clinical Pharmacology, Faculty of Pharmacy with Division of Laboratory Diagnostics, Wroclaw Medical University, Poland

2 Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Wroclaw Medical University, Poland

Abstract

Background. Postoperative nausea and vomiting (PONV) is a common complication after anesthesia and surgery. Ondansetron is one of the most widely used drugs in the prophylaxis of PONV and is extensively metabolized in humans. In vitro metabolism studies have shown that ondansetron is a substrate for human hepatic cytochrome P450 enzymes. The cytochrome P450 (human hepatic cytochrome [CYP]) 2D6 inhibitor quinidine reduced in vitro hydroxylation of ondansetron, which indicates the important role of CYP2D6 in ondansetron metabolism. Genotyping these alleles allows the prediction of the extensive metabolizer (EM) and poor metabolizer (PM) phenotypes with approx. 90–96% accuracy.
Objectives. The aim of our study was to evaluate whether the pharmacological prevention of PONV with ondansetron depends on the most common CYP2D6 alleles (CYP2D6*1, *3, *4, *5, and NxN [multiplication gene]).
Material and Methods. Genotyping for the defective CYP2D6*3, CYP2D6*4 and CYP2D6*5 alleles among 93 surgical female patients was performed by polymerase chain reaction amplification and restriction fragment length polymorphism (PCR-RFLP).
Results. The genetically defined EMs and ultrarapid metabolizers (UMs) of CYP2D6 had a statistically significant (p < 0.02) higher frequency of nausea and vomiting after strumectomy (33.3%) than intermediate metabolizers (IMs) (10.3%) and PMs (0%). The relative risk (odds ratio [OR]) of PONV occurrence was 5 times higher for EMs/UMs than IMs/PMs.
Conclusion. Our results suggest that PONV treatment with ondansetron could be improved by basic, widely available and inexpensive PCR-RFLP genetic tests.

Key words

CYP2D6, ondansetron, postoperative nausea and vomiting

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