Absorption, Distribution and Excretion
Chlordiazepoxide is excreted in the urine, with 1% to 2% unchanged and 3% to 6% as conjugate.
INCR DISAPPEARANCE RATES OF CHLORDIAZEPOXIDE & ITS METABOLITES WERE OBSERVED AFTER SINGLE PRETREATMENT DOSE TO MICE. INCR CLEARANCE WAS INSUFFICIENT TO EXPLAIN TOLERANCE OBSERVED AND THE POSSIBILITY OF ALTERED DRUG DISTRIBUTION BETWEEN BLOOD & BRAIN TISSUE CANNOT BE EXCLUDED.
LEVELS OF (14)C WERE MAX IN TISSUES OF CYNOMOLGUS MONKEYS 2-6 HR AFTER ORAL DOSE OF CHLORDIAZEPOXIDE. BRAIN TO BLOOD CONCN RATIOS OF (14)C WERE GREATER THAN 1. CONCN OF (14)C WERE HIGHEST IN LIVER & KIDNEYS & LOWER IN HEART, LUNGS, SPLEEN, BRAIN, ADRENALS, PANCREAS & FAT. AFTER 24 HR, GI TRACT CONTAINED 15%, TISSUES 33%, URINE 34%, & FECES 1%.
Chlordiazepoxide is absorbed more rapidly and predictably after oral than after intramuscular administration, but blood levels vary widely among individuals.
PLASMA CONCENTRATION-TIME CURVES OF CHLORDIAZEPOXIDE WERE SATISFACTORILY DESCRIBED BY A BI-EXPONENTIAL EXPRESSION CONSISTENT WITH A TWO-COMPARTMENT MODEL SYSTEM AFTER INTRAVENOUS DOSES TO HEALTHY MALE VOLUNTEERS. MEAN HALF-LIFE VALUES OF THE DISTRIBUTION AND ELIMINATION PHASE WERE 0.25 AND 9.4 HOURS, RESPECTIVELY, WHILE MEAN VALUES FOR VOLUMES OF THE CENTRAL COMPARTMENT (V1) AND THE OVERALL DISTRIBUTION (VDBETA) WERE 18 AND 31% OF BODY WEIGHT. DRUG ABSORPTION FROM IM DOSES WAS COMPARATIVELY SLOW AND ADEQUATE DESCRIPTION OF RESULTING PLASMA LEVELS OF CHLORDIAZEPOXIDE REQUIRED THE INCORPORATION OF A TWO-COMPARTMENT "MUSCLE MODEL" WHICH INCLUDED PRECIPITATED AND SOLUBILIZED DRUG IN MUSCLE TISSUE. DISTRIBUTION VOLUMES OF CHLORDIAZEPOXIDE WERE SIGNIFICANTLY LARGER IN FEMALE SUBJECTS THAN IN THE MALES, SUGGESTING MORE EXTENSIVE DRUG DISTRIBUTION AMONG FEMALES. CHLORDIAZEPOXIDE IS TAKEN UP BY THE RED CELLS TO ONLY A LIMITED EXTENT.
For more Absorption, Distribution and Excretion (Complete) data for CHLORDIAZEPOXIDE (9 total), please visit the HSDB record page.

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Metabolism / Metabolites
Hepatic.
IN MAN & DOGS, BIOTRANSFORMATION RESULTS IN SUCCESSIVE HYDROLYSIS OF METHYLAMINO-SUBSTITUENT IN 2-POSITION & HYDROLYTIC FISSION OF RESULTANT LACTAM; 7-CHLORO-1,3-DIHYDRO-5-PHENYL-2H-1,4-BENZODIAZEPINE-2-ONE-4-OXIDE & N-(2-AMINO-5-CHLORO-ALPHA-PHENYL-BENZYLIDENE) GLYCINE-N-OXIDE ARE EXCRETED IN URINE.
IN DOGS, 1% OF A DOSE OF LIBRIUM FOUND IN URINE AS OXAZEPAM GLUCURONIDE AND A FURTHER 1% IN FECES AS FREE OXAZEPAM GLUCURONIDE. THESE MINOR METABOLITES PRESUMABLY ARISE VIA LACTAM BY STEPS INVOLVING REDUCTION OF N-OXIDE FUNCTION.
YIELDS 2-AMINO-7-CHLORO-5-PHENYL-3H-1,4-BENZODIAZEPINE-4-OXIDE IN MAN, IN MONKEY. /FROM TABLE/
YIELDS N-(2-AMINO-5-CHLORO-ALPHA-PHENYLBENZYLIDENE)-GLYCINE-N-OXIDE IN PSEUDOMONAS, IN CLOSTRIDIUM. /FROM TABLE/
... THE MAJOR ACTIVE METABOLITE /OF CHLORDIAZEPOXIDE IS/ DESMETHYLCHLORDIAZEPOXIDE ...
Hepatic.
Route of Elimination: Chlordiazepoxide is excreted in the urine, with 1% to 2% unchanged and 3% to 6% as conjugate.
Half Life: 24-48 hours

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Biological Half-Life
24-48 hours
The elimination half-life of the major active metabolite, desmethylchlordiazepoxide, ranges from one to four days ...
PLASMA CONCENTRATION TIME CURVES OF CHLORDIAZEPOXIDE WERE SATISFACTORILY DESCRIBED BY A BI-EXPONENTIAL EXPRESSION CONSISTENT WITH A TWO COMPARTMENT MODEL SYSTEM AFTER INTRAVENOUS DOSES TO HEALTHY MALE VOLUNTEERS. MEAN HALF-LIFE VALUES OF THE DISTRIBUTION AND ELIMINATION PHASE WERE 0.25 AND 9.4 HOURS, RESPECTIVELY ...
THE DISPOSITION OF CHLORDIAZEPOXIDE (CDP), 50 MG INFUSED IV OVER 10 MINUTES, WAS STUDIED IN NORMAL SUBJECTS AND IN PATIENTS WITH BIOPSY-PROVEN CIRRHOSIS. IN THE NORMAL SUBJECTS, MEAN KINETIC PARAMETER WAS HALF-LIFE (BETA), 10.0 HOURS. VALUE IN CIRRHOTIC PATIENTS WAS HALF-LIFE (BETA), 34.9 HOURS.
Half-life: 5-30 hr /From table/

Toxicity Summary
Chlordiazepoxide binds to stereospecific benzodiazepine (BZD) binding sites on GABA (A) receptor complexes at several sites within the central nervous system, including the limbic system and reticular formation. This results in an increased binding of the inhibitory neurotransmitter GABA to the GABA(A) receptor.BZDs, therefore, enhance GABA-mediated chloride influx through GABA receptor channels, causing membrane hyperpolarization. The net neuro-inhibitory effects result in the observed sedative, hypnotic, anxiolytic, and muscle relaxant properties.

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Toxicity Data
LD50: 537 mg/kg (Oral, Rat) (A308)

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Interactions
Additive sedation or enhanced atropine-like effects reportedly may occur with concomitant use of chlordiazepoxide and a tricyclic antidepressant. Several case reports have appeared describing this interaction.
THE ELIMINATION RATE AND PLASMA CLEARANCE OF CHLORDIAZEPOXIDE MAY BE REDUCED IN WOMEN TAKING ORAL CONTRACEPTIVES.
COMBINED ADMINISTRATION OF ETHANOL (4 G/KG) AND CHLORDIAZEPOXIDE (CDP, 12.5 MG/KG) ON MOUSE BRAIN C-ADENOSINE MONOPHOSPHATE AND C-GUANOSINE MONOPHOSPHATE LEVELS WERE INVESTIGATED. THE COMBINATION DID NOT RESULT IN A SUPRA-ADDITIVE EFFECT ON C-ADENOSINE MONOPHOSPHATE LEVELS. ETHANOL AND CDP TOGETHER INDUCED A SUPRA-ADDITIVE DECREASE OF C-GUANOSINE MONOPHOSPHATE CONCENTRATIONS IN THE CEREBELLUM AT 2 AND 4 HOURS. THIS RESULTED IN A LENGTHENED PERIOD (ABOUT 2.5 HOURS) DURING WHICH THE CEREBELLAR C-GMP LEVELS WERE BELOW 30% OF CONTROL VALUES, AND THIS INTERVAL COINCIDED WITH THE INCREASE IN SLEEP TIME.
MICE WHICH WERE ADMINISTERED CHLORDIAZEPOXIDE (CDP)/ETHANOL HAD SIGNIFICANTLY HIGHER BLOOD AND BRAIN CHLORDIAZEPOXIDE LEVELS THAN MICE INJECTED WITH CHLORDIAZEPOXIDE ALONE. THE INCREASE IN CDP CONCENTRATIONS COULD BE PARTLY RESPONSIBLE FOR THE SUPRA-ADDITIVE PROLONGATION OF ETHANOL SLEEP TIME. THE N-DEMETHYL METABOLITE AND/OR ITS METABOLITES WERE LARGELY RESPONSIBLE FOR THE SUPRA-ADDITIVE EFFECT.
For more Interactions (Complete) data for CHLORDIAZEPOXIDE (9 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 Rat oral 548 mg/kg
LD50 Rat ip 143 mg/kg
LD50 Rat iv 165 mg/kg
LD50 Mouse oral 260 mg/kg
For more Non-Human Toxicity Values (Complete) data for CHLORDIAZEPOXIDE (7 total), please visit the HSDB record page.

Therapeutic Uses
Adjuvants, Anesthesia; Anti-Anxiety Agents, Benzodiazepine; GABA Modulators; Sedatives, Nonbarbiturate
MEDICATION (VET): 15-30% LEVEL IN FEED, PRODUCES ... /CNS DEPRESSION/ IN COWBIRDS; QUAILS (5-10% LEVEL) SHOW EXCITEMENT PHASE BEFORE ... /CNS DEPRESSION/. 3-10 MG/KG IP AGAINST AGGRESSIVE BEHAVIOR IN RATS. AS CNS DEPRESSANT (80 MG/KG) IN RATS & MICE. AS ADRENERGIC BLOCKING AGENT (20 MG/KG) IN MICE. IN ZOO ANIMALS, 4-25 MG/KG BY SUITABLE ROUTE OF ADMIN HAS TAMING EFFECT ON VICIOUS ANIMALS; BARBITURATES ARE USED AS ADJUNCTIVES. IN RHESUS MONKEYS AS ANTICONVULSANT (4.4 MG/KG IV) /FROM TABLE/
Chlordiazepoxide ... is used for ... the management of agitation associated with acute alcohol withdrawal.
... AS PREMEDICATION IN ANESTHESIA & IN OBSTETRICS DURING LABOR. /BENZODIAZEPINES/
For more Therapeutic Uses (Complete) data for CHLORDIAZEPOXIDE (7 total), please visit the HSDB record page.

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Drug Warnings
CHLORDIAZEPOXIDE HYDROCHLORIDE REQUIRES ... PRECAUTIONS REGARDING ITS USE IN PT WITH KNOWN HYPERSENSITIVITY, ELDERLY & EXCESSIVELY DEPRESSED INDIVIDUALS, PREGNANT & LACTATING MOTHERS, PT WITH KNOWN RENAL & HEPATIC IMPAIRMENT, PT ON OTHER CNS DEPRESSANT DRUGS, & IN PT WITH EITHER A HISTORY OF DRUG ADDICTION OR INDISCRIMINANT ALTERATION OF DRUG DOSAGE. /CHLORDIAZEPOXIDE HYDROCHLORIDE/
Safety and efficacy of orally administered chlordiazepoxide ... in children younger than 6 years of age ... have not been established.
The iv preparation reconstituted with 0.9% sodium chloride injection or sterile water for injection should not be given im /SRP: absorption from this site is very slow and variable/ injection.
THE EFFECT OF NORMAL ORAL DOSES (10 MG 3 TIMES A DAY) OF CHLORDIAZEPOZIDE (LIBRIUM) WAS STUDIED IN A DOUBLE-BLIND CROSSOVER TRIAL IN 7 PATIENTS WITH RESPIRATORY FAILURE DUE PREDOMINANTLY TO CHRONIC BRONCHITIS. IN 6 PATIENTS THE DRUG CAUSED A HIGHLY SIGNIFICANT INCREASE IN MIXED VENOUS CARBON-DIOXIDE TENSION AND A SIGNIFICANT FALL IN FORCED EXPIRATORY VOLUME IN ONE SECOND. IT IS CONCLUDED THAT CHLORDIAZEPOXIDE IS CONTRAINDICATED IN PATIENTS WITH RESPIRATORY FAILURE DUE TO CHRONIC BRONCHITIS.
For more Drug Warnings (Complete) data for CHLORDIAZEPOXIDE (13 total), please visit the HSDB record page.

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Pharmacodynamics
Chlordiazepoxide has antianxiety, sedative, appetite-stimulating and weak analgesic actions. The drug seems to block EEG arousal from stimulation in the brain stem reticular formation. The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses. Hostile monkeys were made tame by oral drug doses which did not cause sedation. Chlordiazepoxide revealed a "taming" action with the elimination of fear and aggression. The taming effect of chlordiazepoxide was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.

C16H14CLN3O

299.76

299.082

58-25-3

438-41-5

2712

Yellow crystalline powder
Light yellow plates from ethanol

236-236.5
236-236.5 °C

2.4

48.2

1

3

1

21

580

0

BUCORZSTKDOEKQ-UHFFFAOYSA-N

InChI=1S/C16H14ClN3O/c1-18-15-10-20(21)16(11-5-3-2-4-6-11)13-9-12(17)7-8-14(13)19-15/h2-9,21H,10H2,1H3

7-chloro-4-hydroxy-N-methyl-5-phenyl-3H-1,4-benzodiazepin-2-imine

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。