Absorption, Distribution and Excretion
Unlike baclofen, the absorption of R-baclofen (albaclofen) is not limited to the upper small intestine. The ability of abaclofen to be absorbed throughout the gastrointestinal tract made the development of the sustained-release formulation abaclofenpracarbi (AP) possible. In an AP absorption study in 10 healthy volunteers, subjects orally administered 20 mg AP after a meal, with a time to peak concentration (Tmax) of 5.05 hours. In rats, the oral bioavailability of R-baclofen was 44 ± 12% at an AP dose of 10 mg/kg and 68 ± 6% at a dose of 1 mg/kg. In monkeys and dogs, the oral bioavailability of R-baclofen after oral administration of AP was also high, at 94 ± 16% and 92 ± 7%, respectively. In contrast, the oral bioavailability of R-baprofen in monkeys and dogs was 39 ± 21% and 49 ± 20%, respectively. Colonic absorption studies measured the bioavailability of R-baclofen after intracolonic administration in rats and monkeys. The results showed that the bioavailability of R-baclofen alone was low (7 ± 3% and 3 ± 2%, respectively), while the bioavailability of R-baclofen was significantly improved after intracolonic administration of AP suspension (37 ± 9% in rats and 37 ± 15% in monkeys). Intracolonic administration of AP suspension also resulted in higher bioavailability of R-baclofen in dogs (77 ± 23%). The absorption of R-baclofen in the intestine includes passive and active absorption and is carried out via monocarboxylic acid transporter type 1. 84-88% of R-baclofen is excreted by the kidneys, and less than 1% is excreted in the feces. (2) Radiolabeling showed that AP was widely distributed throughout the body. Its tissue distribution was mainly concentrated in the kidneys and liver. After intravenous injection of AR in rats, the total blood clearance rate was 15.81 ± 10.2 L/h/kg. In contrast, after intravenous injection of R-baclofen in rats, monkeys, and dogs, the half-life was 1.6–3.4 hours, and the total blood clearance was 0.51 ± 0.13 L/h/kg in rats, 0.31 ± 0.11 L/h/kg in monkeys, and 0.24 ± 0.01 L/h/kg in dogs. (2) In a study using a radioactive tracer linked to R-baclofen, 97% of the radioactive material was recovered in urine.

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Metabolism/Metabolites
In experimental studies using human liver S9, abaclofen pracabi was not a substrate of CYP1A2, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. Abaclofen pracabi is an acyloxyalkyl carbamate prodrug of R-baclofen, which is believed to be hydrolyzed by human carboxylesterase-2 to the parent amine R-baclofen. It is expected that carbon dioxide, isobutyric acid, and isobutyraldehyde will also be generated in equimolar amounts. The formation of isobutyric acid has been confirmed in vitro by mass spectrometry and gas chromatography.

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Biological half-life
Intravenous injection of AP in rats showed that the half-life of AP converted to R-baclofen is 6 minutes.

: Erickson CA, Veenstra-Vanderweele JM, Melmed RD, McCracken JT, Ginsberg LD, Sikich L, Scahill L, Cherubini M, Zarevics P, Walton-Bowen K, Carpenter RL, Bear MF, Wang PP, King BH. STX209 (arbaclofen) for autism spectrum disorders: an 8-week open-label study. J Autism Dev Disord. 2014 Apr;44(4):958-64. doi: 10.1007/s10803-013-1963-z. PubMed PMID: 24272415.

Arbaclofen Placerbil is a prodrug of abaclofen, a selective γ-aminobutyric acid (GABA) B-receptor agonist and the R-enantiomer of baclofen. Discovered and patented by XenoPort, it is a novel chemical entity with superior pharmacokinetic characteristics compared to baclofen, enabling sustained release. Arbaclofen Placerbil was initially considered a potential treatment for gastroesophageal reflux disease (GERD) and esophageal adhesion dysplasia; however, due to unsatisfactory clinical trial results, XenoPort abandoned its plans to use the drug for GERD in 2011. On May 20, 2013, XenoPort announced plans to terminate the development of Arbaclofen Placerbil for the treatment of multiple sclerosis.

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Drug Indications
Previously investigated for the treatment of spasms caused by multiple sclerosis, acute back spasms, and gastroesophageal reflux disease.

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Mechanism of Action
It is speculated that R-baclofen helps relieve spasms by acting as an agonist of the inhibitory γ-aminobutyric acid neurotransmission pathway.

C19H26CLNO6

399.8658452034

399.144

847353-30-4

847353-30-4 (Arbaclofen placarbil); 69308-37-8 (Arbaclofen); 63701-55-3 (Arbaclofen hydrochloride)

11281011

Typically exists as solid at room temperature

1.2±0.1 g/cm3

545.1±50.0 °C at 760 mmHg

283.5±30.1 °C

0.0±1.5 mmHg at 25°C

1.523

4.39

2

6

11

27

502

2

CC(C)C(OC(=O)C(C)C)OC(=O)NCC(CC(=O)O)C1=CC=C(C=C1)Cl

JXTAALBWJQJLGN-KSSFIOAISA-N

InChI=1S/C19H26ClNO6/c1-11(2)17(24)26-18(12(3)4)27-19(25)21-10-14(9-16(22)23)13-5-7-15(20)8-6-13/h5-8,11-12,14,18H,9-10H2,1-4H3,(H,21,25)(H,22,23)/t14-,18-/m0/s1

(R)-3-(4-chlorophenyl)-4-((((S)-1-(isobutyryloxy)-2-methylpropoxy)carbonyl)amino)butanoic acid

XP19986 XP-19986 XP 19986 Arbaclofen placarbil.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)