Arbaclofen Placarbil
Arbaclofen Placarbil Uses, Dosage, Side Effects, Food Interaction and all others data.
Arbaclofen Placerbil is a prodrug of Arbaclofen, which is a selective gamma-amino-butyric acid type B receptor agonist and the R-enantiomer of baclofen. It was discovered, and has been patented by XenoPort as a new chemical entity with an improved pharmacokinetic profile compared to baclofen, which allows for sustained release properties.
Arbaclofen Placerbil was believed to have therapeutic potential in treating gastroesophogeal reflux disease (GERD) and plasticity; however due to discouraging clinical trial results, the drug was abandoned by XenoPort in 2011 for the treatment of GERD. On May 20th, 2013, XenoPort announced plans to terminate the development of Arbaclofen Placerbil for the treatment of multiple sclerosis.
| Trade Name | Arbaclofen Placarbil |
| Generic | Arbaclofen Placarbil |
| Arbaclofen Placarbil Other Names | Arbaclofen Placarbil, XP19986 |
| Type | |
| Formula | C19H26ClNO6 |
| Weight | Average: 399.87 Monoisotopic: 399.1448653 |
| Groups | Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Investigated for the treatment of spasticity in multiple sclerosis, acute back spasms, and GERD.
How Arbaclofen Placarbil works
R-baclofen is postulated to aid in spasticity by acting as an agonist of the inhibitory gamma aminobutyric acid neurotransmission pathway.
Volume of Distribution
Radioactive labeling has shown AP to be widely distributed throughout the body. Tissue distribution occurs mostly to the kidneys and liver.
Elimination Route
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.
Half Life
IV bolus administration of AP to rats showed that AP was converted to R-baclofen with a half life of 6 minutes.
Clearance
Blood clearance of an IV bolus of AR in rats resulted in a total blood clearance of 15.81 ± 10.2 L/h/kg in rats.
In comparison, blood clearance of an IV bolus of R-baclofen in rats, monkeys, and dogs, resulted in half lives ranging from 1.6-3.4hours, with total blood clearances reported to be 0.51± 0.13L/h/kg in rats, 0.31±0.11L/h/kg in monkeys, and 0.24L±0.01L/h/kg in dogs. (2)
In studied utilizing radioactive tracers attached to R-baclofen, 97% of radioactivity was recovered in the urine.
Elimination Route
84-88% renal elimination as R-baclofen. Less than 1% fecal elimination. (2)
Innovators Monograph
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