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

Abstract

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·hr/ml; AUC in women 353.6 ± 32.7,561.6 ± 103.6, and 768.7 ± 117.9 ng · hr/ml; maximum concentration (C(max)) in men 45.5 ± 7.0, 40.6 ± 10.4, and 51.2 ± 6.7 ng/ml; C(max) in women 51.4 ± 4.8, 47.1 ± 3.9, and 82.9 ± 6.6 ng/ml. Times to C(max) (T(max); mean ± SEM) for men were 1.5 ± 0.3, 4.4 ± 0.5, and 2.9 ± 0.3 hours; T(max) 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.