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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

  • Clinical Pharmacology
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Abstract

Objective: We compared bolus-infusion with continuous-infusion administration of granisetron antiemetic therapy in patients undergoing haematopoietic stem-cell transplantation.

Methods: We evaluated in a double-blind fashion the efficacy and pharmacokinetics of intravenous bolus-dose granisetron (10 µg/kg bodyweight/day) versus continuous-infusion granisetron (10 µg/kg bodyweight infused over 24 hours) in patients undergoing haematopoietic stem-cell transplantation. Antiemetic therapy was begun within 30 minutes of starting chemotherapy and was continued for 2 days after cytotoxic treatment was completed. All patients also received intravenous dexamethasone 10mg every 12 hours during cytotoxic therapy. Haloperidol 2mg intravenously was permitted as rescue therapy 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) were 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 with rescue antiemetic treatment (haloperidol) was observed in 10 patients in the bolus-dose group compared with three patients in the continuous-infusion group. Failures were noted in five bolus-dose and nine continuous-infusion-treated patients. Granisetron pharmacokinetics were determined in five patients receiving the drug by continuous-infusion and in seven patients after bolus-dose administration. Pharmacokinetic parameter values ranged widely but were similar between the two groups. No relationship between granisetron success or failure and granisetron plasma concentration or pharmacokinetic characteristics was observed.

Conclusion: Continuous-infusion granisetron does not appear to possess any antiemetic superiority to bolus-dose administration in the transplant setting.

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Authors and Affiliations

  1. University Hospitals of Cleveland, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, Ohio, 44106, USA

    Hillard M. Lazarus & Richard J. Creger

  2. Rainbow Babies and Childrens Hospital, Case Western Reserve University, Cleveland, Ohio, USA

    Mary Ann O’Riordan, Carolyn M. Myers, Jeffrey L. Blumer & Michael D. Reed

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  1. Hillard M. Lazarus
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  2. Mary Ann O’Riordan
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  3. Richard J. Creger
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Correspondence to Hillard M. Lazarus.

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Lazarus, H.M., O’Riordan, M.A., Creger, R.J. et al. Pharmacokinetics, Tolerability and Efficacy of Bolus-Dose vs Continuous-Infusion Granisetron in the Prevention of Vomiting in Patients Undergoing Haematopoietic Stem-Cell Transplantation. Clin. Drug Investig. 17, 155–165 (1999). https://doi.org/10.2165/00044011-199917020-00010

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