palonosetron and Body-Weight

Postoperative nausea and vomiting (PONV) is a common postsurgical complication. Palonosetron is effective for PONV prevention at the usual dose of 75 μg, but the ideal dose for obese patients has not yet been investigated. The aim of this study was to compare body weight-adjusted and fixed doses of palonosetron for preventing PONV in obese female patients.. We performed a prospective, randomized, double-blind trial involving 80 female patients, aged 18-80 years with an American Society of Anesthesiologists physical status of 2 and 3 and a body mass index (BMI) ≥ 30 kg m-2 who were scheduled to undergo elective breast surgery. Patients received an intravenous body weight-adjusted dose of palonosetron (1 μg kg -1, GI = 40 patients) or a fixed dose of palonosetron (75 μg, GII = 40 patients). All patients received dexamethasone (4 mg). The incidence of PONV, complete response rate (CR), severity of nausea and need for rescue antiemetics and analgesics were assessed at: 0-1 h, 1-6 h, 6-24 h and 24-48 h postoperatively.. The mean (± SD) BMI was 35.0 (±5.2) kg m-2 for GI and 35.7 (±3.6) kg m-2 for GII. There was no significant difference between groups in PONV incidence, CR, severity of nausea, and need for rescue antiemetics or analgesics. The incidence of PONV for GI and GII was 15% and 27.5%, respectively, during the first 48 h (P = 0.17).. A body weight-adjusted dose of palonosetron was as effective as 75 μg for preventing PONV for 48 h in obese female patients who underwent breast surgery. Hence, the fixed dose may be preferable to the body weight-adjusted dose.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Body Mass Index; Body Weight; Breast; Dexamethasone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Middle Aged; Obesity; Palonosetron; Postoperative Nausea and Vomiting; Prospective Studies; Severity of Illness Index; Young Adult

Palonosetron is the most recent 5-hydroxytryptamine-3 receptor antagonist, and its fixed dose of 0.075 mg is indicated for the prevention of postoperative nausea and vomiting. This study aimed to examine whether fixed dosing is more appropriate than body size-based dosing through the development of a population pharmacokinetic model and model-based simulations.. Fifty-one adult patients undergoing general anesthesia received single intravenous palonosetron administrations 30 min before the end of surgery. Palonosetron concentrations were measured in blood samples collected at various timepoints within 48 h. A population pharmacokinetic analysis was performed by non-linear mixed-effects modeling, and the area under the curves (AUCs) for fixed dosing and body size-based dosing were simulated.. The pharmacokinetics of palonosetron were best described by the three-compartment model, and lean body weight (LBW) was the most significant covariate for all pharmacokinetic parameters. In a patient with LBW of 40 kg, typical clearance and central volume of distribution were 0.102 L/min and 6.98 L, respectively. In simulations, the overall interindividual variability in AUC (0, 48 h) of fixed dosing was not much higher than that of body size-based dosing. In subgroup analysis, the AUCs (0, 48 h) of fixed dosing were considerably lower in the high-weight subgroup and higher in the low-weight subgroup than the median-weight subgroup. In contrast, LBW-based dosing showed similar AUC distributions among the three subgroups.. LBW-based dosing might be suitable for high-weight patients to avoid possible underdosing. Nevertheless, the current fixed dosing of palonosetron is acceptable for adult patients with normal weight.

Topics: Administration, Intravenous; Aged; Anesthesia, General; Area Under Curve; Body Weight; Female; Humans; Male; Middle Aged; Palonosetron; Postoperative Nausea and Vomiting

Palonosetron 75 mcg is being used for the prevention of postoperative nausea and vomiting. However, weight-adjusted doses in laparoscopic surgery are unevaluated.. To determine the response to three doses of palonosetron (0.5, 1.0, or 1.5 mcg kg⁻¹) over 72 h in the postoperative period in women undergoing laparoscopic gynaecological procedures.. A randomised dose-response study.. A tertiary care hospital and research institute in north India from July to December 2014.. American society of Anesthesiologists physical status I and II women, from 18 to 60 years old, undergoing laparoscopic gynaecological procedures on a day care basis.. Patients were randomised to receive palonosetron 0.5, 1 and 1.5 mcg kg⁻¹ intravenously before induction of anaesthesia.. The primary outcome was the proportion of patients with a complete response (i.e. who neither vomited nor required additional antiemetic drugs for nausea during the first 72 postoperative hours). The proportion of patients having nausea or emetic episodes and the requirement for rescue antiemetics and analgesics during the 72-h period were recorded as secondary outcomes.. With palonosetron, there was a significant dose-dependent increase (37.5 vs. 67.5 vs. 75%, P < 0.001) in proportion of patients with a complete response during the 72 h. This was associated with a significant dose-dependent decrease in the proportion of patients with nausea (77.5 vs. 47.5 vs. 35%, P < 0.001) and vomiting (47.5 vs. 32.5 vs. 12.5%, P = 0.003).. Following laparoscopic gynaecological surgery, intravenous palonosetron has a dose-dependent prophylactic effect against postoperative nausea and vomiting during the first 72 postoperative hours.. The trial was registered with Clinical trial registry of India(CTRI/2014/09/004987).

Topics: Administration, Intravenous; Adult; Ambulatory Surgical Procedures; Body Weight; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Dosage Calculations; Female; Gynecologic Surgical Procedures; Humans; India; Isoquinolines; Laparoscopy; Middle Aged; Palonosetron; Postoperative Nausea and Vomiting; Quinuclidines; Serotonin Antagonists; Tertiary Care Centers; Time Factors; Treatment Outcome; Young Adult