Food intake increases the relative oral bioavailability of vanoxerine.
Each of 12 healthy male subjects received single oral doses of 100 mg vanoxerine (GBR 12909), a dopamine reuptake inhibitor with potential antidepressant activity, on three different occasions (fasting, after a low-fat meal and after a high-fat meal) according to a randomized, cross-over design. The mean tmax value increased from 0.82 h after fasting to 1.44 h after a low-fat meal and to 2.46 h after a high-fat meal. Only modest food effects were seen on mean Cmax values (55 nM, 52 nM and 84 nM, after fasting, after the low-fat meal and after the high-fat meal, respectively) but values of AUC up to the last measurable concentration (AUC(0,t)) increased by 76% (from 110 to 194 nM h) after the low-fat meal and by 255% (from 110 to 391 nM h) after the high-fat meal compared with fasting. All of these effects were statistically significant except for the differences in tmax and Cmax between fasting and the low-fat meal. The mechanism of these changes is unclear, but it seems likely that food may lower the first-pass metabolism of vanoxerine, as has been shown for other lipophilic basic drugs.
Ingwersen
S H
SH
Preclinical Development, Novo Nordisk A/S, Maaloev, Denmark.
Mant
T G
TG
Larsen
J J
JJ
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating; D006801:Humans; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010879:Piperazines / Q000008:administration & dosage / Q000493:pharmacokinetics*
D004041:Dietary Fats; D014179:Neurotransmitter Uptake Inhibitors; D010879:Piperazines; C043425:vanoxerine