title: Intestinal absorption of the antiepileptic drug substance vigabatrin in Göttingen mini-pigs is unaffected by co-administration of amino acids.
abstract: 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 0.5-1.0 h (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.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark.
authors.forename: Martha Kampp
authors.initials: MK
authors.lastname: Nøhr
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark; Biologics and Pharmaceutical Science, H. Lundbeck A/S, DK-2500 Valby, Denmark.
authors.forename: René
authors.initials: R
authors.lastname: Holm
authors.affiliation: Department of Bioanalysis, H. Lundbeck A/S, DK-2500 Valby, Denmark.
authors.forename: Zia Irene
authors.initials: ZI
authors.lastname: Thale
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2100 Copenhagen, Denmark. Electronic address: carsten.uhdnielsen@sund.ku.dk.
authors.forename: Carsten Uhd
authors.initials: CU
authors.lastname: Nielsen
mesh_terms: D026905:Amino Acid Transport Systems / Q000378:metabolism*; D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption; D008297:Male; D013552:Swine; D013556:Swine, Miniature; D020888:Vigabatrin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D026905:Amino Acid Transport Systems; D000596:Amino Acids; D000927:Anticonvulsants; D020888:Vigabatrin
keywords: Amino acids; Drug absorption; LYAAT1; Mini-pigs; PAT1; Pharmacokinetic; SLC; SLC36A1; Vigabatrin