Effects of Age and Gender on the Pharmacokinetics of Retigabine
Abstract number :
2.103
Submission category :
Year :
2000
Submission ID :
1562
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Robert Hermann, Geraldine M Ferron, Norbert Knebel, Jeffrey Paul, Lyette S Richards, Peter Russ, Asta Medica, Frankfurt, Germany; Wyeth-Ayerst Research, Radnor, PA.
RATIONALE: To evaluate the effects of age and gender on the pharmacokinetics of oral retigabine. METHODS: Healthy young men (n=12) and women (n=12) aged 18 to 40 years and healthy elderly men (n=12) and women (n=12) aged 66 to 81 years participated in the study. All received a single oral 200-mg dose of retigabine. Serial blood samples were collected over 72 hours after dosing in order to measure concentrations of retigabine and its acetylated metabolite, AWD 21-360. Pharmacokinetic parameters were compared between age groups and gender using analysis of variance. Safety was monitored throughout the study. RESULTS: After administration of a single 200-mg dose of retigabine in young men, retigabine was rapidly absorbed with maximum concentrations occurring within 2.0 hours after dosing. Retigabine was rapidly eliminated following first-order processes with a mean terminal half-life of 8.5 hours and an apparent clearance of 0.67 L/hr/kg. Subjects were similarly exposed to AWD 21-360, which has a lower pharmacologic potency. In young women, retigabine pharmacokinetics were significantly different when compared to young men. Higher maximum concentrations (56%) and exposure (20%) but similar body weight- normalized clearance occurred in young women, indicating that differences in body weight may explain the difference in exposure, and may also partially explain the difference in maximum concentrations. In elderly subjects, retigabine was eliminated more slowly (30% lower weight normalized clearance) thus producing higher exposure (42%) and longer elimination half-life (30%). As retigabine is mainly eliminated by metabolism, these differences may be related to the decrease of the metabolic capacity of the liver with age. Maximum concentrations were not altered by age. Retigabine was well tolerated regardless of age and gender and no serious adverse events were reported. CONCLUSIONS: This study showed that only moderate alterations of retigabine pharmacokinetics occur with age and gender. As retigabine is equally well tolerated in the four groups, no dosage adjustment based on gender and age appears warranted.