TY - JOUR
T1 - Prevention of postoperative nausea and vomiting with granisetron and dolasetron in relation to CYP2D6 genotype
AU - Janicki, Piotr K.
AU - Schuler, H. Gregg
AU - Jarzembowski, Tomasz M.
AU - Rossi, Malina
N1 - Funding Information:
Supported by an Independent Investigator Grant for PKJ from Roche Pharmaceuticals.
PY - 2006/4
Y1 - 2006/4
N2 - We investigated the efficacy of granisetron and dolasetron in preventing postoperative nausea and vomiting. Because the metabolism of the various antiemetic 5-hydroxy tryptamine type 3 (5-HT3) antagonists involves different isoforms of the hepatic cytochrome P450 system, we examined the relationship between the clinical efficacy of these drugs and polymorphic cytochrome P450 2D6 (CYP2D6) genotype. This prospective, randomized, double-blind study involved 150 adult patients with a moderate to high risk for postoperative nausea and vomiting. All subjects received dexamethasone at induction of anesthesia followed by either 12.5 mg of dolasetron or 1 mg of granisetron. We analyzed the number of complete responders (no vomiting or rescue medication) during the first 24 hours after surgery. CYP2D6 genotyping was performed using a TaqMan real-time polymerase chain reaction. A complete response was more frequent in the granisetron group (54.7%) compared with the dolasetron group (38.7%, P < 0.05). In subjects receiving dolasetron, carriers of the duplication of the CYP2D6 allele predicting ultrarapid metabolizer status had more frequent vomiting episodes (P < 0.05) than patients in the granisetron group. It is postulated that the difference in the antiemetic efficacy between two investigated 5-HT3 receptor antagonists may be associated with differences in the carrier status for the duplication of the CYP2D6 allele.
AB - We investigated the efficacy of granisetron and dolasetron in preventing postoperative nausea and vomiting. Because the metabolism of the various antiemetic 5-hydroxy tryptamine type 3 (5-HT3) antagonists involves different isoforms of the hepatic cytochrome P450 system, we examined the relationship between the clinical efficacy of these drugs and polymorphic cytochrome P450 2D6 (CYP2D6) genotype. This prospective, randomized, double-blind study involved 150 adult patients with a moderate to high risk for postoperative nausea and vomiting. All subjects received dexamethasone at induction of anesthesia followed by either 12.5 mg of dolasetron or 1 mg of granisetron. We analyzed the number of complete responders (no vomiting or rescue medication) during the first 24 hours after surgery. CYP2D6 genotyping was performed using a TaqMan real-time polymerase chain reaction. A complete response was more frequent in the granisetron group (54.7%) compared with the dolasetron group (38.7%, P < 0.05). In subjects receiving dolasetron, carriers of the duplication of the CYP2D6 allele predicting ultrarapid metabolizer status had more frequent vomiting episodes (P < 0.05) than patients in the granisetron group. It is postulated that the difference in the antiemetic efficacy between two investigated 5-HT3 receptor antagonists may be associated with differences in the carrier status for the duplication of the CYP2D6 allele.
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U2 - 10.1213/01.ane.0000200364.55798.3f
DO - 10.1213/01.ane.0000200364.55798.3f
M3 - Article
C2 - 16551910
AN - SCOPUS:33645526021
SN - 0003-2999
VL - 102
SP - 1127
EP - 1133
JO - Anesthesia and analgesia
JF - Anesthesia and analgesia
IS - 4
ER -