Pharmacokinetics, tolerability and efficacy of bolus-dose vs continuous-infusion granisetron in the prevention of vomiting in patients undergoing haematopoietic stem-cell transplantation - A randomised, double-blind evaluation

Objective: We compared bolus-infusion with continuous-infusion administrati on of granisetron antiemetic therapy in patients undergoing haematopoietic stem-cell transplantation. Methods: We evaluated in a double-blind fashion the efficacy and pharmaco k inetics of intravenous bolus-dose granisetron (10 mu g/kg bodyweight/day) v ersus continuous-infusion granisetron (10 mu g/kg bodyweight infused over 2 4 hours) in patients undergoing haematopoietic stem-cell transplantation. A ntiemetic therapy was begun within 30 minutes of starting chemotherapy and was continued for 2 days after cytotoxic treatment was completed. All patie nts also received intravenous dexamethasone 10mg every 12 hours during cyto toxic therapy. Haloperidol 2mg intravenously was permitted as rescue therap y in patients who experienced two or more episodes of vomiting within a 24- hour period. Results: Forty-three patients (median age 42 years, range 19 to 65 years) w ere studied: 24 received bolus-dose and 19 continuous-infusion granisetron. Complete success (no vomiting) was observed in nine patients in the bolus- dose group compared with seven in the continuous-infusion group. Success wi th rescue antiemetic treatment (haloperidol) was observed in 10 patients in the bolus-dose group compared with three patients in the continuous-infusi on group. Failures were noted in five bolus-dose and nine continuous-infusi on-treated patients. Granisetron pharmacokinetics were determined in five p atients receiving the drug by continuous-infusion and in seven patients aft er bolus-dose administration. Pharmacokinetic parameter values ranged widel y but were similar between the two groups. No relationship between graniset ron success or failure and granisetron plasma concentration or pharmacokine tic characteristics was observed. Conclusion: Continuous-infusion granisetron does not appear to possess any antiemetic superiority to bolus-dose administration in the transplant setti ng.