A model for evaluating droperidol's effect on the median QTc interval.
Controversy surrounds the use of the antiemetic droperidol, because of the Food and Drug Administration-imposed "black box" warning alleging that even small doses of the drug can lead to serious (even fatal) arrhythmias when it is used for antiemetic prophylaxis during the perioperative period. We used mathematical modeling of electrocardiographic QT interval data published in a peer-reviewed manuscript to evaluate the relationship between the dose of droperidol (0.1-0.25 mg/kg i.v.) and QT(c) prolongation. In comparing the calculated QT(c) values based on the logarithm model (27-63 ms), the linear model (27-67 ms) and the square-root model (36-57 ms) to the actual measured QT(c) values (37-59 ms), the square-root model provided the best simulation of the experimental findings. Other models that we evaluated included the polynomial model and various exponent models (e.g., quartic-root model, cubic-root model, square model, and cubic model). The estimated median prolongation of the median QT(c) interval produced by droperidol 0.625-1.25 mg i.v. would vary from 9 +/- 3 to 18 +/- 3 ms. Therefore, this regression analysis suggests that small "antiemetic" doses of droperidol (< or =1.25 mg) would be unlikely to produce proarrhythmogenic effects in the perioperative period.


CONCLUSIONS
Using a square-root curve fit model to evaluate the relationship between the dose of droperidol and QT(c) prolongation, small-dose droperidol (0.625-1.25 mg i.v.) would be expected to produce <30-ms prolongation of the QT(c) interval. Therefore, small "antiemetic" doses of droperidol would not be expected to produce proarrhythmogenic effects when used for prophylaxis in surgical patients.
Zhang
Yongfeng
Y
New Drug Center at Amphastar Pharmaceuticals Inc., Rancho Cucamonga, California, USA.
Luo
Ziping
Z
White
Paul F
PF
D000465:Algorithms; D000932:Antiemetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004329:Droperidol / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D016014:Linear Models; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D008954:Models, Biological; D015233:Models, Statistical
D000932:Antiemetics; D004329:Droperidol