Relative bioavailability of ondansetron 8-mg oral tablets versus two extemporaneous 16-mg suppositories: formulation and gender differences.

STUDY OBJECTIVE

To compare the relative bioavailability of two 16-mg extemporaneously prepared suppository formulations with that of an 8-mg commercially available oral tablet.

DESIGN

Prospective, crossover bioavailability study.

SETTING

Inpatient clinical research center.

SUBJECTS

Sixteen young, nonsmoking, healthy volunteers.

INTERVENTIONS

Blood samples were obtained 24 and 48 hours after administration of an 8-mg oral ondansetron tablet and 16-mg suppository, respectively. Two 16-mg suppository formulations were compounded using commercially available Fattibase and Polybase.

MEASUREMENTS AND MAIN RESULTS

Ondansetron was well absorbed by both routes of administration. The following pharmacokinetic parameters (mean+/-SEM) were obtained for the 8-mg tablet, 16-mg Fattibase suppository, and 16-mg Polybase suppository, respectively: area under the curve (AUC) in men 154.2+/-21.77, 253.4+/-72.3, 304.8+/-62.2 ng x hr/ml; AUC in women 353.6+/-32.7, 561.6+/-103.6, and 768.7+/-117.9 ng x hr/ml; maximum concentration (Cmax) in men 45.5+/-7.0, 40.6+/-10.4, and 51.2+/-6.7 ng/ml; Cmax in women 51.4+/-.8, 47.1+/-3.9, and 82.9+/-6.6 ng/ml. Times to Cmax (Tmax; mean+/-SEM) for men were 1.5+/-0.3, 4.4+/-0.5, and 2.9+/-0.3 hours; Tmax for women were 1.8+/-0.3, 4.1+/-0.4, and 4.4+/-0.6 hours for the three formulations, respectively. Women had a consistently higher AUC for all three formulations than men (p<0.05).

CONCLUSION

With the exception of the 16-mg Polybase formulation in women, the two suppositories closely approximated the pharmacokinetics of the 8-mg oral tablet. These results suggest that gender may be a significant factor in ondansetron's disposition.