Absorption, Distribution and Excretion
Following oral administration in healthy subjects, the plasma concentration fell by 50% in 24 hours post-administration.
Under physiological conditions, chlorobutanol is unstable. The mean urinary recovery accounts for 9.6% of the dose orally administered.
The volume of distribution was approximately 233 ± 141 L in healthy individuals receiving oral chlorobutanol.
In healthy subjects, the clearance was approximately 11.6 ± 1.0 mL/min following oral administration.

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Metabolism / Metabolites
Chlorobutanol is reported to undergo glucuronidation and sulphation.

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Biological Half-Life
Following oral administration, the terminal elimination half life in healthy subjects was 10.3 ± 1.3 days.

Protein Binding
The binding to plasma proteins was 57 ± 3%.

[1]. Chlorobutanol: maternal serum levels and placental transfer in the mouse. Vet Hum Toxicol. 1997 Oct;39(5):287-90.

[2]. The antibacterial stability of chlorobutanol stored in polyethylene bottles. Am J Hosp Pharm. 1971 Jul;28(7):507-12.

Chlorobutanol is a tertiary alcohol.
Chlorobutanol, or chlorbutol, is an alcohol-based preservative with no surfactant activity. It also elicits sedative-hypnotic and weak local anesthetic actions in addition to antibacterial and antifungal properties. Similar in nature to chloral hydrate, it is formed by the simple nucleophilic addition of chloroform and acetone. As a long-term stabilizer of multi-ingredient preparations, chlorobutanol is normally used at a concentration of 0.5%. At this concentration, it also conserves its antimicrobial activity. Due to the long terminal half-life of 37 days, the use of chlorobutanol as a sedative is limited because of the considerable accumulation which will occur following multiple dosing. Chlorobutanol is a common detergent preservative in eye drops and other ophthalmic therapeutic formulations.
A colorless to white crystalline compound with a camphoraceous odor and taste. It is a widely used preservative in various pharmaceutical solutions, especially injectables. Also, it is an active ingredient in certain oral sedatives and topical anesthetics.
See also: Chlorobutanol; Doxylamine Succinate (component of).

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Drug Indication
No approved therapeutic indications on its own.

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Mechanism of Action
As a detergent, chlorobutanol disrupts the lipid structure of the cell membrane and increases the cell permeability, leading to cell lysis. It induces conjunctival and corneal cell toxicity via causing cell retraction and cessation of normal cytokines, cell movement, and mitotic activity. It disrupts the barrier and transport properties of the corneal epithelium as well as inhibits the utilization of oxygen by the cornea. Chlorobutanol also inhibits oxygen use by the cornea, which increases susceptibility to infection.

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Therapeutic Uses
Adrenergic alpha-Agonists; Adrenergic Agents; Sympathomimetics; Vasoconstrictor Agents
TOPICALLY AS SOLN IN CLOVE OIL AS DENTAL ANALGESIC. IT HAS LOCAL ANESTHETIC POTENCY TO MILD DEGREE & HAS BEEN EMPLOYED AS ANESTHETIC DUSTING POWDER (1 TO 5%) OR OINTMENT (10%).
WHEN ADMIN ORALLY, IT HAS MUCH THE SAME THERAPEUTIC USE AS CHLORAL HYDRATE. HENCE, CHLOROBUTANOL HAS BEEN EMPLOYED AS SEDATIVE & HYPNOTIC. IT HAS BEEN TAKEN ORALLY TO ALLAY VOMITING DUE TO GASTRITIS. DOSE--TOPICAL. ... IN TABLETS OR CAPSULES.
MEDICATION (VET): ANTISEPTIC & LOCAL ANESTHETIC; INTERNALLY, IT IS USED AS SEDATIVE & HYPNOTIC. IT APPEARS TO BE OF VALUE IN GASTRITIS WITH PERSISTENT VOMITING IN DOGS.
For more Therapeutic Uses (Complete) data for CHLORETONE (7 total), please visit the HSDB record page.

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Drug Warnings
VET WARNING: ... NOT FOR USE AS MOTION SICKNESS DRUG IN CATS AS REPEATED USE IN THIS SPECIES CAUSES RESP CENTER DEPRESSION & MAY BE FATAL. AVOID USE IN ANIMALS WITH LIVER OR KIDNEY PATHOLOGY.
RESEMBLES CHLORAL HYDRATE BUT NO GASTRIC IRRITATION.
ALLERGIC REACTIONS ... INCLUDE ERYTHEMA, SCARLATINIFORM EXANTHEMS, URTICARIA, AND ECZEMATOID DERMATITIS. THE ERUPTION USUALLY BEGINS ON THE FACE OR BACK AND SPREADS TO THE NECK, CHEST, AND ARMS; IT MAY BE FOLLOWED BY DESQUAMATION ... /CHLORAL HYDRATE/
UNDESIRABLE CNS EFFECTS INCLUDE LIGHTHEADEDNESS, MALAISE, ATAXIA, & NIGHTMARES. "HANGOVER" ALSO MAY OCCUR ... /CHLORAL HYDRATE/

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Pharmacodynamics
Chlorobutanol is a detergent preservative with a broad spectrum of antimicrobial activity. _In vitro_, chlorobutanol demonstrated to inhibit platelet aggregation and release via unknown mechanisms. A study proposes that the antiplatelet effect of chlorobutanol may occur from inhibition of the arachidonic acid pathway. It attenuated thromboxane B2 formation, elevation of cytosolic free calcium, and ATP release, and additionally exhibited a significant inhibitory activity toward several aggregation inducers in a time- and concentration-dependent manner. Chlorobutanol may exert a direct negative inotropic effect on myocardial cells to isometric tension produced by the heart. Chlorobutanol was shown to induce conjunctival and corneal cell toxicity _in vitro_: at a concentration of 0.1%, Cbl caused near depletion of the squamous layer while degeneration of corneal epithelial cells, generation of conspicuous membranous blebs, cytoplasmic swelling, and occasional breaks in the external cell membrane were observed at a concentration of 0.5%.

175.956

57-15-8

Chlorobutanol hemihydrate;6001-64-5

5977

White to off-white solid powder

1.4±0.1 g/cm3

167.0±0.0 °C at 760 mmHg

~78 °C

61.8±25.9 °C

0.6±0.6 mmHg at 25°C

1.491

2.07

1

1

0

8

83.8

0

ClC(C(C([H])([H])[H])(C([H])([H])[H])O[H])(Cl)Cl

OSASVXMJTNOKOY-UHFFFAOYSA-N

InChI=1S/C4H7Cl3O/c1-3(2,8)4(5,6)7/h8H,1-2H3

1,1,1-trichloro-2-methylpropan-2-ol

Chlortran Methaform Chlorobutanol Acetochlorone

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 (~563.51 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (14.09 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 (14.09 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 (14.09 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.)