Evaluation of Subcutaneous (SC) Versus Intravenous (IV) Palonosetron in Cancer Patients Treated with Platinum-Based Chemotherapy: A Randomized Pharmacokinetic Assay

Background 5-HT3 antagonists are one of the more effective antiemetic preventions in patients who are receiving platinum-based chemotherapy. Some of these 5-HT3 antagonist are available for oral use, however the therapeutic formulations with more bioavailability and middle course which have been traditionally administrated by the intravenous route, have a limited use in the hospital environment. Up to now, no study has examined the pharmacokinetics of these drugs when administered subcutaneously. We have compared pharmacokinetics of palonosetron in the two different routes, SC and IV. Methods Patients under platinum-based chemotherapy were randomized to receive before the first cycle of chemotherapy, palonosetron by the SC or the IV route. In the second cycle, the drug was administrated by the other route. The main endpoint was Area Under the Curve between 0-24 hours (AUC 0–24h). Blood samples were drawn at 10, 15, 30, 45, 60, 90 min and 2, 3, 4, 8, 12, 24 h after palonosetron. Drug levels were determined by HPLC with fluorescence detection after liquid extraction of the samples, with a quantitation limit of 0.1 ng/ml. Results We included 26 patients, from October 2009 to May 2010. We found no statistically differences in the Area Under Curve at 24 hours after the drug administration (AUC 0-24) between both routes. Maximum concentration (Cmax) reached after its administration was significantly lower via the SC route than by IV. The time to reach the Cmax (Tmax) by the SC route was superior than the IV route. The elimination of unmetabolized drug in urine (Ae 24h) was similar in both routes, in the first 24 hours, about 20% of the administered dose. The prevention of early and late emesis was equivalent with both alternatives. Conclusions Palonosetron SC administration showed similar AUC0-24h to that of the IV route, with the same exposure to the drug, and good control in the prevention of early and late emesis, which can benefit the management of outpatient treatments. i.v. (mean ± SD) s.c. (mean ±SD) p-value AUC 0-24h (ngxh/ml) 14,10 ± 6,73 12,68 ± 9,70 0,160 Cmax (ng/ml) 11,88 ± 7,38 1,91 ± 1,09 Tmax (h) 0,04 ± 0,04 0,26 ± 0,13 Ae24h (%) 19,48 ± 9,99 22,24 ± 8,50 0,660 Disclosure All authors have declared no conflicts of interest.