Absorption, Distribution and Excretion
Readily absorbed from the GI tract. Peak plasma concentrations occur within 2-4 hours and the onset of action occurs within one hour. The maximal effect of chlorpropamide is seen 3-6 hours following oral administration.
80-90% of a single oral dose is excreted in the urine as unchaged drug and metabolites within 96 hours.
...EFFECTIVELY ABSORBED FROM GI TRACT ...
Excreted (percentage)...60 /from table/
... 20% excreted unchanged; ... /from table/
Chlorpropamide is readily absorbed from the GI tract following oral administration. Following oral administration of a single dose, the drug is detectable in plasma within 1 hour and peak plasma chlorpropamide concentrations occur within 2-4 hours.
For more Absorption, Distribution and Excretion (Complete) data for CHLORPROPAMIDE (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Up to 80% of dose is metabolized likely through the liver to to 2-hydroxylchlorpropamide (2-OH CPA), p-chlorobenzenesulfonylurea (CBSU), 3-hydroxylchlorpropamide (3-OH CPA), and p-chlorobenzenesulfonamide (CBSA); CBSA may be produced by decomposition in urine. It is unknown whether chlorpropamide metabolites exert hypoglycemic effects.
...METABOLISM OF CHLORPROPAMIDE IS INCOMPLETE, AND ABOUT 20% OF THE DRUG IS EXCRETED UNCHANGED
...SOME HYDROLYTIC BREAKDOWN OF ACTUAL UREA MOIETY HAS BEEN DETECTED, RESULTING IN FORMATION OF SULFONAMIDE DERIV... RECENT EVIDENCE SUGGESTS THIS...TO BE ARTIFACTUAL & NOT A GENUINE METABOLITE...
FOLLOWING PER ORAL ADMIN TO MAN OF TRITIATED CHLORPROPAMIDE...80% OF DOSE WAS EXCRETED...DURING 7-DAY PERIOD. METABOLITES...WERE P-CHLOROBENZENESULFONAMIDE...[(P-CHLOROPHENYL)SULFONYL]UREA... 1-[(P-CHLOROPHENYL)SULFONYL]-3-(2-HYDROXYPROPYL)UREA. ..&.1-[(P-CHLOROPHENYL)SULFONYL]-3-(3-HYDROXYPROPYL)UREA...
...DIABETIC PT WERE ADMIN.../CHLORPROPAMIDE/... AT...250-500 MG...PRODUCTS EXCRETED...INCL.../(P-CHLOROPHENYL)SULFONYLUREA/ (21%)... /P-CHLOROBENZENESULFONAMIDE/ (2%), 2-HYDROXYCHLORPROPAMIDE (55%), & 3-HYDROXYCHLORPROPAMIDE (2%).
For more Metabolism/Metabolites (Complete) data for CHLORPROPAMIDE (6 total), please visit the HSDB record page.
Chlorpropamide has known human metabolites that include p-Chlorobenzene sulfonylurea, 2-hydroxy-chlorpropamide, and 3-hydroxy-chlorpropamide.

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Biological Half-Life
Approximately 36 hours with interindividual variation ranging from 25-60 hours. Duration of effect persists for at least 24 hours.
Chlorpropamid has a long half-life (24 to 48 hours).
Half-life...24-48 /hours/ /from table/

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Chlorpropamide is no longer marketed in the United States. Limited data indicate that amounts of chlorpropamide in breastmilk are unlikely to affect a breastfed infant. Short-acting drugs are generally preferred while breastfeeding a neonate to avoid drug accumulation. Monitor breastfed infants for signs of hypoglycemia such as jitteriness, excessive sleepiness, poor feeding, seizures cyanosis, apnea, or hypothermia. If there is concern, monitoring of the breastfed infant's blood glucose is advisable during maternal therapy with hypoglycemic agents.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Highly bound to plasma proteins.

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Interactions
DRUGS THAT MAY INCR RISK OF HYPOGLYCEMIA...INCL OTHER HYPOGLYCEMIC AGENTS, SULFONAMIDES, PROPRANOLOL, SALICYLATES, PHENYLBUTAZONE, PROBENECID, DICUMAROL, CHLORAMPHENICOL, MAO INHIBITORS, & ALCOHOL. /SULFONYLUREAS/
Allopurinol or its metabolites might compete with chlorpropamide for renal tubular secretion and can result in an increased chlorpropamide effect in an occasional patient.
A disulfiram like reaction, which is characterized primarily by flushing of the face, neck, and arms, may occur with any of the sulfonylureas when alcohol is ingested concurrently ... . /Sulfonylurea antidiabetic agents/
The risk of hypoglycemia may be increased or prolonged when moderate or large amounts of alcohol have been consumed concurrently with sulfonylurea antidiabetic agents use; small amounts of alcohol taken with meals do not usually result in hypoglycemia. /Sulfonylurea antidiabetic agents/
For more Interactions (Complete) data for CHLORPROPAMIDE (19 total), please visit the HSDB record page.

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Non-Human Toxicity Values
LD50 RATS ORAL 2390 MG/KG
LD50 RATS INTRAVENOUS 590 MG/KG
LD50 DOGS INTRAVENOUS 575 MG/KG
LD50 DOGS ORAL 800 MG/KG
LD50 MICE ORAL 1680 MG/KG

Therapeutic Uses
Hypoglycemic Agents
Sulfonylureas are used to control hyperglycemia in NIDDM pt who cannot achieve appropriate control with changes in diet alone. /Sulfonylurea/
...EFFECTIVE IN MATURITY-ONSET DIABETIC PT IN WHOM PANCREAS RETAINS CAPACITY TO SECRETE INSULIN. /SULFONYLUREAS/
MEDICATION (VET): IN DIABETES MELLITUS IN DOGS.
For more Therapeutic Uses (Complete) data for CHLORPROPAMIDE (8 total), please visit the HSDB record page.

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Drug Warnings
...STUDIES...INDICATE INCR INCIDENCE OF...DIFFICULTIES IN PT TAKING ORAL HYPOGLYCEMIC DRUG. ...VENTRICULAR TACHYCARDIA &...FIBRILLATION WERE NOTED...USUALLY DURING EARLY STAGES OF MYOCARDIAL INFARCTION... /SULFONYLUREA/
SULFONYLUREAS SHOULD BE ADMINISTERED WITH CAUTION TO PT WITH EITHER RENAL OR HEPATIC INSUFFICIENCY /SULFONYLUREAS/
VET: AVOID USE IN PREGNANT ANIMALS.
VET: /SULFONYLUREA SUBSTANCES/...HAVE BEEN OF LITTLE VALUE IN CANINE DIABETES TREATMENT. ONLY MILDEST CASES HAVE RESPONDED AT ALL. /HYPOGLYCEMIC SULFONYLUREA/
For more Drug Warnings (Complete) data for CHLORPROPAMIDE (18 total), please visit the HSDB record page.

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Pharmacodynamics
Chlorpropamide, a second-generation sulfonylurea antidiabetic agent, is used with diet to lower blood glucose levels in patients with diabetes mellitus type II. Chlorpropamide is twice as potent as the related second-generation agent glipizide.

C10H13CLN2O3S

276.74

276.033

94-20-2

2727

White to off-white solid powder

1.4±0.1 g/cm3

433.5±47.0 °C at 760 mmHg

128 °C

216.0±29.3 °C

0.0±1.1 mmHg at 25°C

1.585

2.8

2

3

4

17

345

0

RKWGIWYCVPQPMF-UHFFFAOYSA-N

InChI=1S/C10H13ClN2O3S/c1-2-7-12-10(14)13-17(15,16)9-5-3-8(11)4-6-9/h3-6H,2,7H2,1H3,(H2,12,13,14)

1-(4-chlorophenyl)sulfonyl-3-propylurea

Diabinese; Chloropropamide; Chlorpropamide

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)

DMSO : ≥ 100 mg/mL (~361.35 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.03 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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