Correlation of anti-emetic efficacy and plasma levels of ondansetron.
Intravenous ondansetron was administered at doses from 0.01 to 0.48 mg/kg every 4 h for three doses to patients receiving cisplatin 60-120 mg/m2 for the first time. Plasma samples were collected from 28 patients at baseline and at suitable times post-dose for pharmacokinetic analysis, and were assayed for ondansetron by high-pressure liquid chromatography. Plasma trough level was defined as the level before the third dose and 4 h area-under-the-curve (AUC4) was calculated with the linear trapezoidal method. Despite wide inter-patient variation, a correlation was seen between both trough level (r = 0.737, P less than 0.0001) and AUC4 (r = 0.903, P less than 0.001) related to dose. Trough level was also predictive of AUC4 (r = 0.824, P less than 0.0001). Frequency of complete protection (no emetic episodes) was equivalent throughout the AUC4 range, suggesting anti-emetic activity even at low AUC4. However, a trend toward better protection against failure (5 or more episodes) was seen when higher values of AUC4 were achieved, suggesting more consistent anti-emetic activity at moderate to high AUC4.
Grunberg
S M
SM
Division of Medical Oncology, University of Southern California Comprehensive Cancer Center, Los Angeles 90033.
Groshen
S
S
Robinson
D C
DC
Stevenson
L L
LL
Sanderson
P E
PE
D000328:Adult; D000368:Aged; D002945:Cisplatin / Q000009:adverse effects; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D017294:Ondansetron; D012702:Serotonin Antagonists; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D007093:Imidazoles; D012702:Serotonin Antagonists; D017294:Ondansetron; D002945:Cisplatin