Influence of administration vehicles and drug formulations on the pharmacokinetic profile of lamotrigine in rats.
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.
Castel-Branco
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MM
Laboratory of Pharmacology, Faculty of Pharmacy, Coimbra University, Coimbra, Portugal.
Figueiredo
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IV
Falcão
A C
AC
Macedo
T R A
TR
Caramona
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MM
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
D000927:Anticonvulsants; D014677:Pharmaceutical Vehicles; D012996:Solutions; D013535:Suspensions; D014227:Triazines; D014867:Water; D000077213:Lamotrigine