Absorption, Distribution and Excretion
After oral or rectal administration, pentobarbital has an onset of action of 10–30 minutes. After intravenous administration of pentobarbital sodium, pentobarbital has an almost immediate onset of action, while pentobarbital sodium has a shorter onset of action. Approximately 40% to 60% of pentobarbital is bound to plasma proteins. In two healthy subjects, after administration of radiolabeled pentobarbital, 79% to 92% was recovered in urine within 6 days, while only 4% to 5% was recovered in feces. Almost no unmetabolized drug was detected in urine and feces. Gas chromatography analysis of body fluids and tissue specimens from 30 autopsy subjects detected pentobarbital sodium (amomobarbital), butobarbital sodium (butobarbital), pentobarbital sodium (pentobarbital), quinabarbital sodium (secobarbital), and their corresponding hydroxylated metabolites. In cases of single barbiturate ingestion, an inverse relationship was observed between drug lipid solubility and its distribution in body fluids and tissues. In most cases, the highest concentration of barbiturates was observed in the liver, with the highest concentrations in the spleen in other cases. Concentrations in bile were generally higher than those in the corresponding liver. In most subjects, the levels of metabolites of these four sedative barbiturates in body fluids and tissues were generally lower than the parent drug concentration, but the concentration of metabolites in urine was generally much higher, sometimes even exceeding the concentration of the parent drug in the liver. Concomitant administration of two or more barbiturates did not appear to affect the distribution and metabolism of the individual drugs.
For more complete data on the absorption, distribution, and excretion of amobarbital (17 in total), please visit the HSDB records page.

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Metabolism/Metabolites
Amobarbital is metabolized in the liver, with the penultimate oxidation step of its 3-methylbutyl substituent yielding tertiary hydroxyamobarbital, which is an inactive metabolite. Approximately 40-50% of orally administered hypnotic doses of amobarbital are excreted in the urine as hydroxyamobarbital and its glucuronide conjugates. Less than 1% of the oral hypnotic dose is excreted unchanged in the urine. Conjugates of hydroxypentobarbital (which may be excreted in feces or urine) and/or other unidentified oxidation products may constitute the residual dose. In two healthy subjects who received radiolabeled pentobarbital… less than 50% of the dose was identified as 3'-hydroxypentobarbital. A second major metabolite was identified as N-hydroxypentobarbital, present in up to 30% of the dose. The relative proportions of pentobarbital metabolites in urine vary considerably, and observations of plasma half-life cannot reflect this variation. Metabolic patterns in specific individuals can be effectively estimated by studying single urine samples from the post-distribution phase. Two metabolites were detected in urine samples from the post-distribution phase. The two metabolites are the side-chain hydroxylated product 3'-hydroxyamoebabital and the glucono-conjugated N-β-D-glucopyranosylamoebabital. N-hydroxyamoebabitalone was synthesized, and its urinary content in 13 subjects who received 200 mg of amobarbital sodium was investigated. The conclusion was that the excretion of free N-hydroxyamoebabitalone was not significant in the metabolism of amobarbital sodium. /Sodium pentobarbital/ For more complete metabolite/metabolite data on pentobarbital (8 metabolites), please visit the HSDB record page.

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Biological half-life
After intravenous bolus injection of pentobarbital, plasma concentrations decreased in a biphasic manner. The first phase half-life was approximately 40 minutes, and the second phase half-life was 20-25 hours, but the range of the second phase half-life varied from 14 to 42 hours among different patients. The half-life of pentobarbital was studied in 36 unrelated subjects; the half-life (23.8 hours) was normally distributed. Following intramuscular injection of 200 mg sodium pentobarbital into mothers with mild hypertension 0.7 to 3.5 hours before delivery, the half-life of pentobarbital in neonatal plasma was 2.5 times that of the mother. /Sodium pentobarbital/

Toxicity Summary
Pentobarbital (like all barbiturates) exerts its effects by binding to the α or β subunits of the GABA_A receptor. These binding sites differ from those of GABA itself and benzodiazepines. Similar to benzodiazepines, barbiturates enhance the effects of GABA on this receptor. This GABA_A receptor binding reduces input resistance, inhibits burst and tetanic discharges, particularly in neurons of the ventral basal ganglia and intralaminar nuclei, while increasing burst duration and mean conductance of individual chloride channels; this increases the amplitude and decay time of inhibitory postsynaptic currents. In addition to this GABAergic effect, barbiturates also block AMPA receptors, a subtype of the glutamate receptor. Glutamate is a major excitatory neurotransmitter in the mammalian central nervous system. Amobarbital also appears to bind to neuronal nicotinic acetylcholine receptors.

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Interactions
To determine the effects of human growth hormone (GH) on human metabolism, we administered 3–5 mg of amobarbital sodium orally three times weekly to six children with growth hormone deficiency. The half-life of amobarbital sodium increased from 13.89 hours to 22.75 hours, with no change in volume of distribution and a decrease in clearance. These results indicate that GH slowed the metabolism of amobarbital sodium, possibly by affecting the hepatic microsomal drug oxidation system. /Amobarbital Sodium/
Concomitant use of disulfiram and barbiturates may inhibit the metabolism of barbiturates and increase the incidence of barbiturate toxicity. Concomitant use of barbiturates with carbamazepine or succinimide anticonvulsants may lead to accelerated metabolism, resulting in decreased serum concentrations and a shortened elimination half-life due to enhanced hepatic microsomal enzyme activity. Monitoring serum concentrations is recommended to guide dose adjustments, especially when adding or discontinuing carbamazepine or succinimide anticonvulsants to an existing treatment regimen. Concomitant use of barbiturates with cyclophosphamide, especially phenobarbital, may induce microsomal metabolism, increasing the production of cyclophosphamide alkylating metabolites, thereby shortening the half-life of cyclophosphamide and enhancing its leukopenic effect. /Barbiturates/
For more complete data on interactions of amobarbital (39 in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in rats: 250 mg/kg
Intraperitoneal LD50 in rats: 115 mg/kg /Amobarbital sodium/
Subcutaneous LD50 in rats: 190 mg/kg
Oral LD50 in mice: 345 mg/kg
For more complete data on non-human toxicity values of amobarbital (9 in total), please visit the HSDB record page.

Therapeutic Uses
GABA modulators; sedatives, barbiturates. Pentobarbital (discontinued in the US) and sodium pentobarbital are primarily used as hypnotics for short-term treatment of insomnia, with treatment durations up to two weeks… These drugs are also used for routine sedation, anxiety relief, and preoperative sedation. Sodium pentobarbital can be used to… control acute agitated episodes of psychosis (such as catatonic psychosis, pessimistic psychosis, or manic reactions), but its value in the long-term treatment of psychosis is limited. Injectable sodium pentobarbital can also be used for anesthesia analysis, anesthetic treatment, and as an adjunct to the diagnosis of schizophrenia. /Experimental Therapy:/…Preoperative screening for temporal lobe epilepsy (TLE) includes intracarotid artery pentobarbital injection (IAP), i.e., two consecutive injections of pentobarbital on the ipsilateral and contralateral sides of the epileptic focus. We investigated whether bilateral IAP is more advantageous than unilateral ipsilateral IAP. Methods: This population-based study included 183 consecutive patients who underwent bilateral intraperitoneal aspiration (IAP) during TLE surgical screening. We used a multivariate model to assess the added value of bilateral IAP on surgical decisions, resection extent, amygdalae and hippocampus resection, postoperative seizure freedom, memory performance, and changes in IQ. Results: Based on the results of unilateral IAP, bilateral IAP had additional prognostic value for changes in postoperative verbal memory (P < 0.01) and verbal IQ (P < 0.01), especially in patients with left-sided lesions. Conversely, the information provided by contralateral IAP was not related to decision-making or surgical strategy. Conclusion: Bilateral IAP has added value in predicting postoperative verbal memory and IQ. Currently, bilateral IAP is not used to guide surgical strategies, but it can be used for this purpose when verbal abilities are particularly concerning in patients with left-sided lesions. In other cases, unilateral IAP is the best option.
Medications (Veterinary): ...primarily used for its hypnotic or sedative effects. Amobarbital Sodium /

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Drug Warnings
Amobarbital (discontinued commercially in the US) and amobarbital sodium have the toxicity of barbiturates and should be treated according to standard precautions for barbiturate use.
Susceptible patients may develop barbiturate-alcohol dependence after taking any sedative-hypnotic drug… This is characterized by a strong need to continue taking the drug, a tendency to increase the dose, psychological dependence on the drug's effects, and physiological dependence on the drug's effects to maintain homeostasis, and a characteristic withdrawal syndrome upon discontinuation. /Hypnotics and Sedatives/
Veterinarians: Avoid concurrent use of chloramphenicol, as chloramphenicol significantly prolongs the duration of anesthesia in mice.
Intravenous administration of pentobarbital sodium may cause respiratory depression, apnea, or hypotension, especially if administered too quickly. Administration must be slow, not exceeding 100 mg/min, and personnel and equipment should be readily available for artificial respiration. The safety and efficacy of pentobarbital and pentobarbital sodium in children under 6 years of age have not been established. For more complete data on drug warnings for pentobarbital (29 in total), please visit the HSDB records page.

C11H18N2O3

226.27

226.131

57-43-2

64-43-7 (hydrochloride)

2164

Crystals
White, crystalline powder

313 to 316 °F (NTP, 1992)

2.1

2

3

4

16

303

0

VIROVYVQCGLCII-UHFFFAOYSA-N

InChI=1S/C11H18N2O3/c1-4-11(6-5-7(2)3)8(14)12-10(16)13-9(11)15/h7H,4-6H2,1-3H3,(H2,12,13,14,15,16)

2,4,6(1H,3H,5H)-Pyrimidinetrione, 5-ethyl-5-(3-methylbutyl)-

Barbamyl acidAmobarbital AmybalAmobarbitale Amylbarbitone Binoctal

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.)