Anesth Analg 2003;97:1857
© 2003 International Anesthesia Research Society
LETTERS TO THE EDITOR
Is There Rationale to Use an Antiemetic in the Same Class for the Treatment of Patients Who Experience Postoperative Nausea and Vomiting Despite Prophylaxis?
Anthony L. Kovac, MD
Department of Anesthesiology, University of Kansas Medical Center, Kansas City, Kansas
To the Editor:
Current therapy of patients who have postoperative nausea and vomiting (PONV) despite prophylaxis is to switch to a different antiemetic from another class (1). A redosing study (2) determined that when intraoperative prophylactic ondansetron was unsuccessful, repeating it in the PACU did not have additional efficacy. Redosing studies in chemotherapy-induced nausea and vomiting (CINV) (3–5) suggest changing to a different member of the same 5-hydroxytryptamine (5-HT3) antagonist class allows increased efficacy.
Although the 5-HT3 antagonists have structural similarities to serotonin, there are side chain differences. Granisetron’s effectiveness for failed ondansetron CINV patients may be related to side chain differences and increased receptor binding. Granisetron is highly specific (1000:1) for the 5-HT3 receptor, but ondansetron also has nonspecific binding to 5-HT1A and 5-HT1B (6). Granisetron has a longer plasma half-life versus ondansetron (4.9 to 7.7 h (7) vs 3.5 to 5.5 h (8), respectively). Ondansetron’s metabolism is affected by variations of the cytochrome P450 CYP2D6 genotype, with ultrarapid metabolism causing decreased response to ondansetron (9).Granisetron is metabolized by CYP3A, not CYP2D6 (10), suggesting that granisetron may be able to rescue within class. Whether this observation is transferable from CINV to PONV, from ondansetron to other same-class members and vice versa, suggests lessons from the CINV model and merits a PONV study.
References
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- Kovac AL, O’Connor TA, Pearman MH, et al. Efficacy of repeat intravenous dosing of ondansetron in controlling postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled multicenter trial. J Clin Anesth 1999; 11: 453–9.[Web of Science][Medline]
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- de Wit R, de Boer AC, vd Linden GH, et al. Effective cross-over to granisetron after failure to ondansetron, a randomized double-blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy. Br J Cancer 2001; 85: 1099–101.[Web of Science][Medline]
- van Wijngaarden I, Tulp MT, Soudijn W. The concept of selectivity in 5-HT receptor research. Eur J Pharmacol 1990; 188: 301–12.[Web of Science][Medline]
- Kytril (granisetron hydrochloride) injection prescribing information. Nutley, NJ: Roche Pharmaceuticals, December 2000.
- Zofran (ondansetron hydrochloride) injection full prescribing information. Research Triangle Park, NC: GlaxoSmithKline, September 2001.
- Kaiser R, Sezer O, Papies A, et al. Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotypes. J Clin Oncol 2002; 20: 2805–11.[Abstract/Free Full Text]
- Bloomer JC, Baldwin SJ, Smith GJ, et al. Characteristics of the cytochrome P450 enzymes involved in the in vitro metabolism of granisetron. Br J Clin Pharmacol 1994; 38: 557–66.[Web of Science][Medline]
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