title: Influence of administration vehicles and drug formulations on the pharmacokinetic profile of lamotrigine in rats.
abstract: Given that administration vehicles and drug formulations can affect drug bioavailability, their influence on the pharmacokinetic profile of lamotrigine (LTG), a new-generation anti-epileptic drug, was studied in rats. Three different formulations administered intraperitoneally at a dose of 10 mg/kg were used: (1) LTG suspended in a 0.25% methylcelulose solution, (2) LTG dissolved in a 50% propylene glycol solution, and (3) LTG isethionate dissolved in distilled water. Plasma and brain homogenate levels were determined in order to evaluate vehicle-dependent drug absorption. The results demonstrated rapid absorption of LTG when it was administered as an aqueous solution, in contrast to a slower and more erratic absorption after the injection of either the lipophilic solution or the suspension. A plasma peak was achieved 15 min post-dose with the aqueous solution, with a brain peak being achieved 15 min later, while with the other formulations both plasma and brain homogenate peaks were reached 2 h after LTG administration. This study suggests that LTG isethionate dissolved in distilled water is the most suitable formulation for successful LTG pharmacokinetic studies in rats.
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmacy, Coimbra University, Coimbra, Portugal.
authors.forename: M M
authors.initials: MM
authors.lastname: Castel-Branco
authors.forename: I V
authors.initials: IV
authors.lastname: Figueiredo
authors.forename: A C
authors.initials: AC
authors.lastname: Falcão
authors.forename: T R A
authors.initials: TR
authors.lastname: Macedo
authors.forename: M M
authors.initials: MM
authors.lastname: Caramona
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D001921:Brain / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D007274:Injections, Intraperitoneal; D000077213:Lamotrigine; D008297:Male; D014677:Pharmaceutical Vehicles; D051381:Rats; D017208:Rats, Wistar; D012996:Solutions; D013535:Suspensions; D014227:Triazines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014867:Water
chemical_list: D000927:Anticonvulsants; D014677:Pharmaceutical Vehicles; D012996:Solutions; D013535:Suspensions; D014227:Triazines; D014867:Water; D000077213:Lamotrigine