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

Abstract

SummaryWe investigated whether the 2677G>T ⁄ A and 3435C>T polymorphisms of adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) affect the efficacy of ondansetron to prevent postoperative nausea and vomiting. One hundred and ninety-eight patients undergoing general anaesthesia were enrolled. Thirty minutes before the end of surgery, 0.1 mg.kgondansetron was administered intravenously. The incidence of postoperative nausea and vomiting was compared between genotypes in the 2677G>T ⁄ A and 3435C>T polymorphisms of ABCB1. The incidence of postoperative nausea and vomiting was lower in patients with the 2677TT genotype (TT vs Non-TT = 25.9% vs 53.0%, p = 0.01) and 3435TT genotype (CC + CT vs TT = 52.6% vs 21.7%, p = 0.01) during the first 2 h after surgery. There were no significant differences in the incidence of postoperative nausea and vomiting between the different genotype groupings during period between 2 and 24 h after surgery. In conclusion, ABCB1 genotypes may be a clinical predictor of responsiveness for ondansetron. Postoperative nausea and vomiting (PONV) is a common and distressing complication in patients undergoing general anaesthesia. The incidence ranges between 20% and 30%, but is as high as 80% in high-risk patients [1] and may cause significant complications [2]. Although the exact mechanism of PONV is not clear, it is known that the chemoreceptor trigger zone in the area postrema plays an important role, in which the 5-hydroxytryptamine type-3 (5-HT 3 ) receptor is involved in the occurrence of PONV [3].Currently, 5-HT 3 receptor antagonists such as ondansetron are widely used for prevention and treatment of PONV and although these agents have a significant effect, over 35% of patients treated with ondansetron may still experience PONV [4,5]. We hypothesised that polymorphism in the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1), an encoding gene of transporter for ondansetron in the brain-blood barrier [6], would contribute to such inter-individual variation.In a previous study, the 3435C>T single nucleotide polymorphism of ABCB1 was associated with the efficacy of 5-HT 3 receptor antagonists for chemotherapy-induced nausea and vomiting [7]. Therefore, we investigated whether the 2677G>T ⁄ A, and 3435C>T polymorphisms of ABCB1 affect the efficacy of ondansetron in preventing PONV in patients undergoing general anaesthesia. MethodsThis study was approved by the Institutional Review Board of Yonsei University Hospital. Written informed consent was obtained from each patient. One hundred and ninety-eight adult patients, of ASA physical status 1-2, undergoing laparoscopic cholecystectomy were enrolled in this study. Patients with a history of drug abuse, known hypersensitivity to 5-HT 3 receptor antagonist, body mass index > 30 kg.m , hepatic or renal disease or who had used antiemetics within the 24 h before the study were excluded. Before surgery, all patients were interviewed about their medical history including tobacco use, presence of PONV and motion sic...

Influence of ABCB1 and ABCG2 polymorphisms on the antiemetic efficacy in patients with cancer receiving cisplatin-based chemotherapy: a TRIPLE pharmacogenomics study

“…Previous study reported by Choi et al demonstrated that all ABCB1 3435C4T polymorphisms had no significant differences on the efficacy of ondansetron for postoperative nausea and vomiting during the period between 2 and 24 h after surgery. 19 The other report demonstrated that no significant association was found between CR and ABCB1 3435C4T polymorphism in the breast cancer patients treated with granisetron. 19 However, there was a trend toward higher response to 5-HT 3 receptor antagonists in the ABCB1 3435TT, although it was not statistically significant.…”

“…19 The other report demonstrated that no significant association was found between CR and ABCB1 3435C4T polymorphism in the breast cancer patients treated with granisetron. 19 However, there was a trend toward higher response to 5-HT 3 receptor antagonists in the ABCB1 3435TT, although it was not statistically significant. In this study, aprepitant was added to the 5-HT 3 receptor and dexamethasone.…”

“…14,15 Moreover, there are several reports showing that polymorphisms of the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) transporter protein are also associated with CINV and postoperative nausea and vomiting. [16][17][18][19][20] However, these investigations were on the basis of first-generation 5-HT 3 receptor antagonists, such as ondansetron and granisetron, without neurokinin-1 receptor antagonist, and there are conflicting reports on the effects of ABCB1 polymorphisms. Furthermore, in these studies, the use of antiemetic medications, such as dexamethasone, was not in accordance with the antiemetic guidelines.…”

Correlation of MDR1 gene polymorphisms with anesthetic effect of sevoflurane–remifentanil following pediatric tonsillectomy

“…[13] Till date many single-nucleotide polymorphisms (SNPs) have been identified in the exons of MDR1, among which, 1236C > T, 2677G > T/A, and 3435C > T in MDR1 are the main variants which are investigated repeatedly in different countries and races worldwide under multiple disease conditions. [14–16] MDR1 is known to be an important transporter which constrains the accumulation of many drugs, such as chemotherapeutic and antiepileptic drugs. [14] …”

Postoperative nausea and vomiting

“…The most common types of genetic study associated with PONV are those of the single nucleotide polymorphisms associated with neural signaling and transmitter receptors in the PONV system. Genes regarded as related to PONV or OINV include 5-HT 3 (subunit A and B) receptor [7], muscarinic type 3 receptor, dopamine type 2 receptors [8], catechol-o-methyl-transferase [9], alpha 2 adrenoceptors [10], adenosine triphosphate-binding cassette subfamily B member 1 [11], cytochrome P450 superfamily enzyme [12], and UDP-glucuronosyltransferase.…”