1 Pharmaceutical Design and Drug Delivery, Department of Pharmacy, Faculty of Health and Medical Sciences, Københavns Universitet2 Drug Research Academy A, Drug Research Academy, Faculty of Pharmaceutical Sciences, Københavns Universitet3 Det Teknisk-Naturvidenskabelige Fakultet, Aalborg Universitet4 Department of Bioanalysis, H. Lundbeck A/S, DK-2500 Valby, Denmark.5 Department of Pharmacy, Faculty of Pharmaceutical Sciences, Københavns Universitet6 Drug Research Academy A, Drug Research Academy, Faculty of Pharmaceutical Sciences, Københavns Universitet7 Department of Pharmacy, Faculty of Pharmaceutical Sciences, Københavns Universitet
The anti-epileptic drug substance vigabatrin is used against infantile spasms. In vitro evidence suggests that vigabatrin is transported via the proton coupled amino acid transporter (PAT1). The aim of the present study was to investigate whether the intestinal absorption of vigabatrin in vivo was mediated via PAT1 in non-rodents. This was investigated by oral co-administration of vigabatrin and PAT1-ligands to Göttingen mini-pigs. Vigabatrin had an oral absorption fraction (Fabs) of 75-80%, and the maximal plasma concentration (Cmax) was reached within 0.5-1.0h (tmax). Co-administration of vigabatrin and amino acids generally did not significantly affect Fa, Tmax or Cmax. However, co-administration with sarcosine prolonged the time to reach Cmax. After co-administration with amino acids, vigabatrin absorption showed a slightly lowered onset. This may indicate an effect of amino acids on either the rate of gastric emptying or an effect directly on the absorption of vigabatrin, possibly via inhibition of PAT1 or another drug transporter. In conclusion, co-administration of PAT1-ligands together with vigabatrin did not significantly alter the pharmacokinetic profile of vigabatrin.
International Journal of Pharmaceutics, 2014, Vol 466, Issue 1-2, p. 18-20