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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.

Long-acting propranolol (Inderal LA) is a new formulation of propranolol that allows release of the drug in a controlled manner, so that the plasma concentration at 24 hr after dosing is greater with long-acting propranolol than with conventional tablets. A single dose of 160 mg of long-acting propranolol can produce cardiac beta-adrenoceptor blockade throughout a 24 hr period without variability due to multiple peak concentrations. It has been shown that this formulation is as effective in the treatment of angina pectoris, hypertension and hyperthyroidism as the standard formulation. Studies with long-acting propranolol in cardiac dysrhythmias are lacking. This new dosage form would be a means of simplifying dosing regimens and thereby hopefully enhancing patient convenience and compliance.

The antihypertensive effect of doxazosin 1-16 mg once-daily was compared with that of atenolol 50-100 mg once-daily, and placebo, utilizing a double-blind parallel group (12 patients each) design. Blood pressure (BP) and pulse rate were determined in out-patients who returned for clinic visits every 2 weeks for 14 weeks. During the first 4 weeks, all patients received single-blind placebo therapy. During the subsequent 10 weeks, patients were randomized to placebo, atenolol or doxazosin treatment. After 2 weeks of doxazosin therapy 16 mg daily, there was a significant decrease from baseline (single-blind placebo period) in supine diastolic BP (P less than 0.01) and standing diastolic BP (P less than 0.001). The decreases in supine and standing diastolic BPs in the doxazosin 16 mg daily group were significantly (P less than 0.01) different from the corresponding BPs of the placebo group. At weeks 12 and 14, heart rates in the doxazosin group were not significantly different from baseline or from those in the placebo group. After 4 and 6 weeks of atenolol 100 mg daily, there was a significant decrease from baseline in both supine (P less than 0.001 and P less than 0.05) and standing (P less than 0.05) diastolic BPs and heart rates (P less than 0.05). However, when the atenolol group was compared with the placebo group, a significant decrease occurred only with supine diastolic BP at week 12 (P less than 0.01) and not at week 14; but significant decreases occurred in supine and standing heart rates at weeks 12 and 14 (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)