Arbaclofen Placarbil

Unlike baclofen, absorption of R-baclofen(arbaclofen) is not limited to the upper small intestine. The ability of arbaclofen to be absorbed throughout the gastrointestinal tract allowed for the development of the sustained release formulation, arbaclofen placarbil (AP). In one study of AP absorption in 10 healthy volunteers, one 20mg oral dose of AP, in the presence of food, resulted in a Tmax of 5.05h. The oral bioavailability of R-baclofen in rats when AP was dosed at 10mg/kg was 44 ± 12%, and when dosed at 1mg/kg, oral bioavailability was 68 ± 6%. In monkeys and dogs, the oral bioavailability of R-baclofen when AP was orally dosed was high: 94 ± 16%, and 92 ± 7%, respectively. In comparison, when oral R-balofen was dosed oral bioavailability was 39 ± 21% in monkeys and 49 ± 20% in dogs. Colonic absorption studies measuring R-baclofen bioavailability post intracolonic dosing in rats and monkeys, have revealed low bioavailability with the administration of R-baclofen (7 ± 3% and 3 ± 2%, respectively), and significantly higher R-baclofen bioavailability with intracolonic dosing of AP suspension ( 37 ± 9% and 37 ± 15%, in rats and monkeys respectively). Intracolonic dosing of AP suspension also resulted in high biolavailability of R-baclofen in dogs (77 ± 23%). Absorption throughout the intestine is both passive and active and occurs via the monocarboxylate type 1 transporter.