Abstracts

Levetiracetam (LEV) is an antiepileptic drug used for treatment of partial seizures in humans. LEV is available as oral tablets and syrup and an intravenous (IV) formulation (100 mg/mL) is under review at the FDA. The purpose of this pilot study was to obtain data regarding the pharmacokinetics and absolute bioavailability of intramuscular (IM) LEV in dogs to lay the foundation for human studies., The experiments were done on 6 Hound dogs weighing approximately 22 kg. All dogs received 500 mg (5 mL of IV formulation of LEV) intramuscularly. Three dogs received 500 mg of IV LEV and 3 dogs received 250mg of IV LEV after which the IV catheter was withdrawn and an additional 250 mg was instilled around the vein as an approximation of extravasation. This procedure was done to evaluate the change in pharmacokinetics due to extravasation during IV dosing. A wash out period was allowed between intramuscular and intravenous dosing. Samples were collected starting at 15 min through 24 h at predetermined time intervals. Plasma LEV was detected by reversed phase high performance liquid chromatography. The pharmacokinetic parameters were estimated by non-compartmental analysis., LEV was completely absorbed after intramuscular administration with a bioavailability of 100%. The median time to achieve maximum plasma concentration (Cmax) after IM dosing was 30 min, and the observed Cmax was 6.13 [plusmn] 0.51 [micro]g/mL. After IV injection, LEV showed evidence of mono-exponential elimination with a half-life of 174 [plusmn] 19 min, a volume of distribution of 2.7 L/kg and a clearance of 258 [plusmn] 41 mL/min. Extravasation did not alter LEV pharmacokinetics following IV administration., LEV demonstrated rapid absorption and complete bioavailability in dogs after intramuscular administration. Extravastation around the IV site did not appear to alter LEV pharmacokinetics. These characteristics, in combination with evidence of safety and tolerability, suggest that LEV should be evaluated for Intramuscular administration in humans., (Supported by UCB Pharma.)