Influence of obesity on pharmacokinetics and analgesic effect of ketoprofen administered intravenously to patients after laparoscopic cholecystectomy.

Abstract

Ketoprofen is an analgesic drug commonly applied in the postoperative period, e.g., to patients after laparoscopic cholecystectomy. Many patients who undergo this procedure are obese. As pathophysiological changes are observed in obesity, the efficacy of ketoprofen may be altered in this group of patients. The aim of the study was to compare the pharmacokinetic parameters and analgesic effect of ketoprofen administered to obese and non-obese patients after laparoscopic cholecystectomy. The study was conducted on 41 patients after laparoscopic cholecystectomy, who were divided into two groups: obese (n = 21) and non-obese (n = 20). Ketoprofen was administered intravenously at a dose of 100mg. Plasma ketoprofen concentrations were measured by means of validated high-performance liquid chromatography with ultraviolet detection. The pharmacokinetic parameters of the drug were calculated using the non-compartmental method. Additionally, pain intensity was assessed during the study using NRS scale. The obese patients had significantly lower AUC0-∞ (1.4-fold), AUMC0-t (1.8-fold), AUMC0-∞ (3.2-fold), MRT0-t (1.4-fold), MRT0-∞ (2.3-fold), t0.5 (2.3-fold) and Vz/kg (2.3-fold) and higher kel (2.2-fold) than the non-obese group. Moreover, 4h and 6h after the administration of the drug, pain intensity was significantly higher in the obese patients. The drug was eliminated faster and the analgesic effect of ketoprofen in the obese patients was decreased as compared with the non-obese subjects. However, pain intensity did not increase to the level, which required additional analgesic treatment. Therefore, it seems that dosage adjustment of intravenous ketoprofen is not necessary in obese patients.