ANTIEMETIC EFFICACY AND PHARMACOKINETICS OF INTRAVENOUS ONDANSETRON INFUSION DURING CHEMOTHERAPY CONDITIONING FOR BONE-MARROW TRANSPLANT

We investigated the antiemetic efficacy and safety of intravenous onda nsetron infusion in the BMT setting. We conducted prospective randomiz ed comparison trials between ondansetron at 2 dose levels and metoclop ramide (MCP) plus droperidol for the prevention of chemotherapy-induce d nausea and vomiting in 2 patient populations scheduled to undergo BM T. One patient population (n = 30) received CY alone, the other popula tion (n = 30) received combination chemotherapy of Bu and CY, The CY a lone group received ondansetron for 3 days, and the Bu/CY group receiv ed ondansetron for 7 days. The primary endpoints were emesis control a nd nausea. Secondary endpoints included acute (headache, diarrhea and sedation) and delayed (engraftment and regimen-related) side-effects, In both trials, ondansetron provided better emesis control than did MC P plus droperidol during CY administration (P = 0.009, 3-day trial; P = 0.0022, 7-day trial). There was a wide interpatient variation in ser um ondansetron levels, although group averages were proportional to th e dose administered. Intrapatient day-to-day variation was 10-30% and did not change significantly with concurrent CY administration. Antiem etic efficacy did not correlate with ondansetron serum levels at the d oses tested. Headache incidence was similar in all groups, Sedation wa s highest in the MCP plus droperidol group (P = 0.048, 3-day trial; P = 0.016, 7-day trial). No statistically significant differences in eng raftment or regimen-related toxicities were observed between groups in either trial. Ondansetron appears to be a safe and efficacious antiem etic during conditioning for BMT.