Age and gender effects on ondansetron pharmacokinetics: Evaluation of healthy aged volunteers

Abstract

Modest differences in the clearance of the 5HT3 antagonist, ondansetron, among different age groups were detected in two groups of healthy elderly volunteers, one group aged 61 to 74 years ("elderly") and the other 75 to 82 ("aged") years, in addition to young healthy subjects. Both a single 0.15 mg/kg intravenous dose and a single 8 mg oral dose were administered according to a randomized crossover design with a minimum 3-day washout period between treatments. Mean plasma clearance decreased (young, 0.349 L/hr/kg; elderly, 0.279 L/hr/kg; aged, 0.214 L/hr/kg; p less than 0.05) with increasing age. Volume of distribution at steady state was unaffected by age (young, 1.81 L/kg; elderly, 1.94 L/kg; aged, 1.71 L/kg), resulting in increases in mean plasma half-life (young, 3.4 hours; elderly, 4.5 hours; aged, 5.4 hours) and mean absolute bioavailability (young, 57%; elderly, 61%; aged, 69%) with increasing age. Female subjects cleared ondansetron more slowly than males (p less than 0.05), resulting in higher absolute bioavailability. Ondansetron was well tolerated by all age groups with no increase in the number of adverse events observed in older volunteers.

Additive anti-emetic efficacy of prophylactic ondansetron with droperidol in out-patient gynecological laparoscopy

“…Ondansetron, on the other hand, has a half-life of approximately 3.4 hr. 26 Therefore, the coupling of the longer duration of action of ondansetron with the quicker onset of action of droperidol makes these two drugs an attractive anti-emetic combination.…”

The pharmacokinetics of ondansetron after intravenous injection in healthy volunteers phenotyped as poor or extensive metabolisers of debrisoquine.

“…The pharmacokinetics of ondansetron in healthy volunteers, including the elderly, and in patients with hepatic impairment, have been described previously [2][3][4].…”

Relationships between Ondansetron Systemic Exposure and Antiemetic Efficacy and Safety in Cancer Patients Receiving Cisplatin

“…This regi men produces C[4h] concentrations ranging from 30 to 80 ng/ml [8], Based on the results reported above, this degree of ondansetron systemic exposure ensures good efficacy for most patients. However, our results also sug gest that regimens with higher initial ondanse tron doses for patients receiving high-dose cis platin chemotherapy may provide greater ef ficacy.…”

“…Ondansetron is eliminated from the body by oxidative metabolism, renal clearance ac counting for only 3% of total body clearance [7], Large intersubject variation occurs in the systemic plasma clearance of ondansetron, leading to a wide range of systemic plasma exposures (as measured by AUC) among sub jects receiving the same dosage of ondanse tron [8]. If plasma ondansetron is in equilib rium with the drug at the 5HT3 receptor sites, and if ondansetron mediates its antiemetic effect through antagonism of serotonin at these receptors in humans, then there should exist a relationship between indices of sys temic ondansetron exposure (i.e.…”