Absorption, Distribution and Excretion
Topically, chlorhexidine is unlikely to undergo any degree of systemic absorption. Orally administered chlorhexidine, such as that found in oral rinses for dental purposes, is very poorly absorbed from the gastrointestinal tract - the Cmax in human subjects following an oral dose of 300mg was 0.206 µg/g and occurred approximately 30 minutes after ingestion (Tmax). Following the insertion of 4 PerioChips in 18 adult patients, no detectable plasma or urine chlorhexidine levels were observed.
Excretion of chlorhexidine gluconate occurs almost exclusively via the feces, with less than 1% of an ingested dose excreted in the urine.
34 newborn infants who had been bathed in a standard manner with Hibiscrub were studied to find out whether it was absorbed percutaneously. Low levels of chlorhexidine were found in the blood of all 10 babies sampled by heel prick, and 5 of 24 from whom venous blood was taken. /Chlorhexidine gluconate/
Percutaneous absorption of the antimicrobial agent chlorhexidine (labelled with carbon-14) was studied in rats. Less than 5% of the topically applied chlorhexidine was absorbed during a 5-day period. Excretion of absorbed radioactivity occurred mainly in the feces.
The percutaneous absorption of chlorhexidine gluconate (chlorhexidine digluconate; Hibitane) through hairless rat skin with or without stratum corneum was studied. For tests carried out on whole skin, storage in cutaneous structures after 48 hr was more important than diffusion; the reverse was observed for stripped skin. When the skin was stripped, the amount absorbed was multiplied by approximately 100, and the amount stored in skin by approximately 10. The difference in chlorhexidine diffusion observed between whole and stripped skin was related to the physicochemical characteristics of chlorhexidine. /Chlorhexidine gluconate/
To evaluate the elimination kinetics of chlorhexidine in milk when used as an intramammary infusion to stop lactation in cows. ... The study was performed in 2 phases. Three cows were studied in each phase. All cows were treated with chlorhexidine suspension by infusion into a mastitic mammary gland quarter after 2 milkings 24 hours apart. Foremilk samples (100 mL) were collected from treated and untreated (controls) mammary gland quarters of each cow. Chlorhexidine was extracted from raw milk, and residue concentrations were quantified by use of high-performance liquid chromatography. Foremilk samples from days 2, 5, and 8 were analyzed in phase I, and samples from time 0 and days 3, 7, 14, 21, 28, 35, and 42 were analyzed in phase II. In phases I and II, there was no quantifiable transference of chlorhexidine to milk in untreated mammary gland quarters. Measurable chlorhexidine residues were found in milk from treated mammary gland quarters of 2 cows throughout the 42-day sample period in phase II. Estimated mean elimination half-life for chlorhexidine in milk was 11.5 days.

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Metabolism / Metabolites
As chlorhexidine is very poorly absorbed in the gastrointestinal tract, it is unlikely to undergo metabolic conversion to any significant extent.

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Biological Half-Life
To evaluate the elimination kinetics of chlorhexidine in milk when used as an intramammary infusion to stop lactation in cows. ... The study was performed in 2 phases. Three cows were studied in each phase. All cows were treated with chlorhexidine suspension by infusion into a mastitic mammary gland quarter after 2 milkings 24 hours apart. Foremilk samples (100 mL) were collected from treated and untreated (controls) mammary gland quarters of each cow. Chlorhexidine was extracted from raw milk, and residue concentrations were quantified by use of high-performance liquid chromatography. Foremilk samples from days 2, 5, and 8 were analyzed in phase I, and samples from time 0 and days 3, 7, 14, 21, 28, 35, and 42 were analyzed in phase II. In phases I and II, there was no quantifiable transference of chlorhexidine to milk in untreated mammary gland quarters. Measurable chlorhexidine residues were found in milk from treated mammary gland quarters of 2 cows throughout the 42-day sample period in phase II. Estimated mean elimination half-life for chlorhexidine in milk was 11.5 days.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Chlorhexidine has been used vaginally or topically on the abdomen or perineum prior to delivery to prevent infection. No toxicity has been reported in breastfed infants and it has clearly less toxicity compared to povidone-iodine in these situations. Topical application of chlorhexidine to the breast before and after nursing did not appear to adversely affect the breastfed infants in one study. Use of chlorhexidine oral rinse by a nursing mother is unlikely to adversely affect her infant.
◉ Effects in Breastfed Infants
A group of investigators in Belgium reviewed the results of infant thyrotropin levels on day 5 postpartum in 4745 newborn infants delivered over a 2-year period at their hospital. Infants were divided among those whose mothers had iodine overload (n = 3086) from topical povidone-iodine 10% solution during labor and delivery and those whose mothers had no iodine overload (n = 1659). Mothers had povidone-iodine applied either as a single application to 900 square cm for epidural anesthesia or 3 applications to the entire abdominal wall for cesarean section. Breastfed infants whose mothers had iodine overload had a greater risk for having elevated thyrotropin levels and requiring recall for retesting (3.2% with cesarean section and 2.7% with epidural anesthesia) compared to those who did not (0.1%). Bottle-fed infants were affected much less than breastfed infants. After replacing povidone-iodine with chlorhexidine 0.5% in 70% isopropanol for disinfection for 6 months, 1178 infants that were delivered at this institution had no increased rate of elevations in thyroid function tests and a reduced rate of recalls in breastfed infants.
In a study of mothers in Spain who received 10% povidone-iodine (n = 21) or chlorhexidine (n = 13) topically to the perineum starting immediately before the final stage of labor and daily postpartum to the episiotomy, no differences in thyrotropin, thyroxine or free thyroxine was found among their breastfed infants at day 5 to 7 postpartum.
Studies in Africa have used chlorhexidine vaginally prior to delivery in an attempt to reduce the frequency of mother-to-child transmission (MTCT) of HIV. In one, cotton soaked in 0.25% chlorhexidine solution was used to swab the vaginal walls every 4 hours from admission into labor until delivery in 4078 women. The other study used 120 mL of either 0.2% or 0.4% chlorhexidine solution as a vaginal lavage every 3 hours from admission to labor until delivery in 309 women. The average number of lavages was 2.1 (range 1 to 11). Chlorhexidine 0.25% swabs reduced MTCT in patients whose membranes ruptured more than 4 hours before delivery, but not in other women. Vaginal lavage showed a statistically nonsignificant trend towards reduction of MTCT, with the 0.4% greater than the 0.2%. Almost all of the infants in these studies were breastfed. No adverse events were reported in the infants, but follow-up related primarily to infant mortality and HIV status rather than effects of chlorhexidine.
◉ Effects on Lactation and Breastmilk
A randomized study compared 0.2% chlorhexidine in alcohol to distilled water as a spray to the breast in 200 mothers who were nursing newborns. The mothers sprayed their breasts with the liquid before and after each feeding. Mothers and infants were assessed at discharge and weekly thereafter. Discomfort and nipple trauma were less frequent in the chlorhexidine group than in the placebo group, particularly at the first assessment. Although skin flora on the breasts of the treated mothers was reduced, there was no difference in the frequency of mastitis between the treated and placebo groups. No obvious side effects occurred in the breastfed infants and there were no differences in the rates of oral thrush in infants between the treatments. A systematic review concluded that this practice is not justified based on current evidence.

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Protein Binding
Chlorhexidine is known to bind albumin in both serum and saliva, though the extent of this binding is unclear.

[1]. Peritoneal Lavage Using Chlorhexidine Gluconate at the End of Colon Surgery Reduces Postoperative Intra-Abdominal Infection in Mice. J Surg Res. 2015 May 1;195(1):121-7.

[2]. Assessment of the cytotoxicity of chlorhexidine by employing an in vitro mammalian test system. Journal of Dental Sciences. Volume 9, Issue 2, June 2014, Pages 130-135.

[3]. Differential actions of chlorhexidine on the cell wall of Bacillus subtilis and Escherichia coli. PLoS One. 2012;7(5):e36659.

Chlorhexidine gluconate is an organochlorine compound and a D-gluconate adduct. It has a role as an antibacterial agent. It is functionally related to a chlorhexidine.
Chlorhexidine is a broad-spectrum antimicrobial biguanide used as a topical antiseptic and in dental practice for the treatment of inflammatory dental conditions caused by microorganisms. It is one of the most common skin and mucous membrane antiseptic agents in use today. The molecule itself is a cationic bis-guanide consisting of two 4-chlorophenyl rings and two biguanide groups joined by a central hexamethylene chain. Topical chlorhexidine for disinfection, as well as oral rinses for dental use, carries activity against a broad range of pathogens including bacteria, yeasts, and viruses. Chlorhexidine was developed in the UK by Imperial Chemical Industries in the early 1950s and was introduced to the US in the 1970s. The FDA withdrew its approval for the use of chlorhexidine gluconate topical tincture 0.5%, due to a significant number of reports concerning chemical and thermal burns associated with the use of this product. Other formulations of chlorhexidine continue to be available.
Chlorhexidine is a biguanide compound used as an antiseptic agent with topical antibacterial activity. Chlorhexidine is positively charged and reacts with the negatively charged microbial cell surface, thereby destroying the integrity of the cell membrane. Subsequently, chlorhexidine penetrates into the cell and causes leakage of intracellular components leading to cell death. Since gram positive bacteria are more negatively charged, they are more sensitive to this agent.
Chlorhexidine Gluconate is the gluconate salt form of chlorhexidine, a biguanide compound used as an antiseptic agent with topical antibacterial activity. Chlorhexidine gluconate is positively charged and reacts with the negatively charged microbial cell surface, thereby destroying the integrity of the cell membrane. Subsequently, chlorhexidine gluconate penetrates into the cell and causes leakage of intracellular components leading to cell death. Since gram positive bacteria are more negatively charged, they are more sensitive to this agent.
See also: Chlorhexidine Gluconate; Isopropyl Alcohol (component of); Alcohol; Chlorhexidine Gluconate (component of); Benzethonium chloride; chlorhexidine gluconate (component of) ... View More ...

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Drug Indication
Chlorhexidine is available over-the-counter in various formulations (e.g. solution, sponge, cloth, swab) as a topical antiseptic to sanitize prior to surgeries and/or medical procedures. Dental formulations, available by prescription only, include an oral rinse indicated for the treatment of gingivitis and a slow-release "chip" which is inserted into periodontal pockets and is indicated for the reduction of pocket depth in adult patients with periodontitis as an adjunct therapy to dental scaling and root planing procedures.
FDA Label

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Mechanism of Action
Chlorhexidine’s broad-spectrum antimicrobial effects are due to its ability to disrupt microbial cell membranes. The positively charged chlorhexidine molecule reacts with negatively charged phosphate groups on microbial cell surfaces - this reaction both destroys the integrity of the cell, allowing leakage of intracellular material, and allows chlorhexidine to enter the cell, causing precipitation of cytoplasmic components and ultimately cell death. The specific means of cell death is dependent on the concentration of chlorhexidine - lower concentrations are bacteriostatic and result in leakage of intracellular substances such as potassium and phosphorous, whereas higher concentrations are bactericidal and cause cytoplasmic precipitation.

C28H40CL2N10O7

699.59

896.319

18472-51-0

Chlorhexidine dihydrochloride;3697-42-5;Chlorhexidine;55-56-1;Chlorhexidine diacetate;56-95-1;Chlorhexidine acetate hydrate;206986-79-0

9552081

Colorless to light yellow liquid

1.06 g/mL at 25 °C(lit.)

699.3ºC at 760 mmHg

134ºC

376.7ºC

0mmHg at 25°C

18

16

23

60

819

8

N=C(NC(NCCCCCCNC(NC(NC1=CC=C(Cl)C=C1)=N)=N)=N)NC2=CC=C(Cl)C=C2.O[C@H]([C@@H](O)C(O)=O)[C@H](O)[C@H](O)CO.O[C@H]([C@@H](O)C(O)=O)[C@H](O)[C@H](O)CO

YZIYKJHYYHPJIB-UUPCJSQJSA-N

InChI=1S/C22H30Cl2N10.2C6H12O7/c23-15-5-9-17(10-6-15)31-21(27)33-19(25)29-13-3-1-2-4-14-30-20(26)34-22(28)32-18-11-7-16(24)8-12-18;2*7-1-2(8)3(9)4(10)5(11)6(12)13/h5-12H,1-4,13-14H2,(H5,25,27,29,31,33)(H5,26,28,30,32,34);2*2-5,7-11H,1H2,(H,12,13)/t;2*2-,3-,4+,5-/m.11/s1

(1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexyl]-1-[amino-(4-chloroanilino)methylidene]guanidine;(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoic acid

Chlorhexidine digluconate UniseptChlorhexidine Gluconate Peridex GibitanUNII-MOR84MUD8E Hexidine Hibiclens Hibident Hibisol HibitaneHibiscrub Perio Chip

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)

H2O : ~100 mg/mL (~111.39 mM)
DMSO : ≥ 38 mg/mL (~42.33 mM)

Solubility in Formulation 1: 100 mg/mL (111.39 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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