RELATIVE BIOAVAILABILITY OF ONDANSETRON 8-MG ORAL TABLETS VERSUS 2 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-m g commercially available oral tablet. Design. Prospective, crossover b ioavailability study. Setting. Inpatient clinical research center. Sub jects. Sixteen young, nonsmoking, healthy volunteers. Interventions. B lood 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 avai lable Fattibase and Polybase. Measurements and Main Results. Ondansetr on was well absorbed by both routes of administration. The following p harmacokinetic parameters (mean +/- SEM) were obtained for the 8-mg ta blet, 16-mg Fattibase suppository, and 16-mg Polybase suppository, res pectively: 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 wom en 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 con sistently higher AUC for all three formulations than men (p<0.05). Con clusion. With the exception of the 16-mg Polybase formulation in women , the two suppositories closely approximated the pharmacokinetics of t he 8-mg oral tablet. These results suggest that gender may be a signif icant factor in ondansetron's disposition.