title: Population pharmacokinetics of ramosetron.
abstract: Ramosetron is a selective serotonergic 5-hydroxy-tryptamine receptor 3 antagonist that is used to prevent and treat postoperative nausea and vomiting. This study aimed to characterize the population pharmacokinetics of ramosetron in patients undergoing surgery with general anesthesia. Patients aged 19-80 years received a single intravenous bolus of ramosetron (0.3, 0.45, or 0.6 mg) 30 min before the end of surgery. Blood samples were collected, and plasma concentrations of ramosetron were measured by high performance liquid chromatography-tandem mass spectrometry. Pooled data from 50 patients and 479 pharmacokinetic samples were used for population pharmacokinetic analysis using the nonlinear mixed effect modeling program (NONMEM(®)). The pharmacokinetics of ramosetron was best described by a three-compartment mammillary model with first-order elimination. Based on allometric principles, body weight was incorporated in the base model, along with fixed allometric exponents. The typical value of clearance was 0.19 L/h in a 60-kg subject, and it decreased approximately 3% for every year of age, starting at age of 57. The bootstrap method and visual predictive check showed that the final pharmacokinetic model was appropriate. A population pharmacokinetic model of ramosetron was constructed in adult surgical patients, providing a foundation for further defining the relationship between ramosetron dose and postoperative nausea and vomiting.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, 160, Baekseo-ro, Dong-gu, Gwangju, South Korea.
authors.forename: Seong Heon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, 160, Baekseo-ro, Dong-gu, Gwangju, South Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, 160, Baekseo-ro, Dong-gu, Gwangju, South Korea.
authors.forename: Kyung Yeon
authors.initials: KY
authors.lastname: Yoo
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School, 160, Baekseo-ro, Dong-gu, Gwangju, South Korea. anesman@gmail.com.
authors.forename: Seongwook
authors.identifier: http://orcid.org/0000-0002-1958-8436
authors.initials: S
authors.lastname: Jeong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000758:Anesthesia / Q000009:adverse effects; D001562:Benzimidazoles / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001835:Body Weight; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008326:Mammillary Bodies / Q000378:metabolism; D008875:Middle Aged; D017711:Nonlinear Dynamics; D011153:Population; D020250:Postoperative Nausea and Vomiting / Q000517:prevention & control; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D001562:Benzimidazoles; D058831:Serotonin 5-HT3 Receptor Antagonists; C071315:ramosetron
keywords: NONMEM; Population pharmacokinetics; Postoperative nausea and vomiting; Ramosetron; Serotonin 5-HT3 receptor antagonist