Absorption, Distribution and Excretion
In healthy subjects under fed conditions, oral administration of 20 g of lactitol resulted in a mean time to peak concentration (Tmax) of 3.6 ± 1.2 h, a peak concentration (Cmax) of 776 ± 253 ng/mL, and a mean area under the curve (AUC) of 6,019 ± 1,771 ngh/mL. Lactitol is hardly absorbed in the gastrointestinal tract. Most of the ingested dose is likely degraded into organic acids in the colon and excreted in feces. Data on the volume of distribution of lactitol are not available. Data on lactitol clearance are not available. Three male rats (150–200 g; 6–8 weeks old; one untreated, two acclimated to a diet containing 7% lactitol) were administered approximately 2 mg of D-(sorbitol-1-(14)C) lactitol orally. In studies of lactitol-adapted rats, 9-15% of the radioactivity was recovered from exhaled breath within 0-5 hours, and 48% within 0-24 hours. Small amounts of the injected radioactive material were found in urine and feces (2.3% in urine after 5 hours and 6.8% after 24 hours; 11.7% in feces after 24 hours). The gastrointestinal tract contained 33% radioactivity after 5 hours and 5% after 24 hours; other parts of the body contained 20% radioactivity after 5 hours and 9% after 24 hours. The study concludes that lactitol is extensively degraded in rats after oral administration, likely primarily mediated by the gut microbiota; and that adaptation to unlabeled lactitol in rats did not significantly affect the rate or extent of degradation. In a study aimed at investigating erythritol metabolism in healthy volunteers and comparing in vitro fermentation of erythritol, glucose, and lactitol in human fecal microbiota, four male and two female volunteers (aged 21–25 years) were randomly assigned to receive a single dose of 25 g of (13)C-erythritol, (13)C-glucose, and (13)C-lactol (dissolved in 250 mL of water) after an overnight fast, with intervals of at least three days between doses. Breath samples were collected before and every 30 minutes after administration for analysis of (13)C-carbon dioxide and hydrogen. The ratio of 13C to 12C-carbon dioxide was determined by isotope ratio mass spectrometry. Urine samples were collected at 0–6 hours and 6–24 hours after administration, and the concentrations of erythritol and lactitol in the urine were determined by high-performance liquid chromatography (HPLC). ...At 6 and 24 hours post-administration, 52% and 84% of the administered erythritol were recovered in the urine, respectively. No increase in exhaled ¹³C-carbon dioxide or hydrogen was observed, indicating no intestinal fermentation. Conversely, exhaled ¹³C-carbon dioxide increased rapidly after glucose ingestion, but increased slowly after lactitol ingestion. Hydrogen excretion in exhaled breath also increased after lactitol treatment. No significant amounts of lactitol or glucose were detected in the urine. ...
This study investigated the gastrointestinal absorption of lactitol in 6 healthy volunteers and 8 patients with cirrhosis. Lactitol was not detected in serum after administration of 0.5 g/kg. Urinary lactitol excretion within 24 hours ranged from 0.1% to 1.4% of the administered dose (0.46% in patients with cirrhosis and 0.35% in healthy volunteers). No increase in blood D-lactic acid, L-lactic acid, or plasma glucose levels was observed after lactitol administration. The data indicate that lactitol is poorly absorbed in the gastrointestinal tract in healthy volunteers and patients with cirrhosis, and that this disaccharide does not affect glucose or lactate homeostasis. This study investigated the metabolism of lactitol (a non-absorbable sugar) in six healthy subjects by tracking three metabolic pathways of universally labeled 14C sugars. Six healthy volunteers took 20 grams of lactitol daily for 14 consecutive days. On the seventh day, they simultaneously took 10 microcuries of L-[U-(14)C]-lactol and unlabeled lactitol, and the excretion of (14)C in breath, urine, and feces was monitored. (14)CO2 excretion peaked at 6 hours, with total (14)CO2 accounting for 62.9% (5.0%) of the given isotope, while 6.5% (3.6%) and 2.0% (0.3%) of the marker were recovered in feces and urine, respectively. These data indicate that lactitol is extensively metabolized in the human colon, and a significant portion of bacterial metabolites are absorbed by the colon. Calculations showed that the subjects utilized 54.5% of the compound's theoretical energy. ...

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Metabolism/Metabolites
Since lactitol is hardly absorbed systemically, significant metabolism is unlikely to occur. In a study aimed at investigating erythritol metabolism in healthy volunteers and comparing in vitro fermentation of erythritol, glucose, and lactitol in human fecal microbiota, four male and two female volunteers (aged 21–25 years) underwent overnight fasting and were then randomly assigned to receive a single dose of 25 g of (13)C-erythritol, (13)C-glucose, and (13)C-lactol (dissolved in 250 mL of water), with intervals of at least three days between doses. Breath samples were collected every 30 minutes before and after administration for analysis of (13)C-carbon dioxide and hydrogen. The ratio of 13C to 12C-carbon dioxide was determined using isotope ratio mass spectrometry. … To maintain a constant metabolic rate, subjects remained at rest throughout the study. For in vitro fermentation experiments, fecal samples were collected from six healthy volunteers (sex and age not specified) who consumed a normal Western diet. All subjects were free of gastrointestinal symptoms and had not used antibiotics in the past six months. Samples were incubated anaerobically for 6 hours, and then the hydrogen concentration in the headspace of the culture flasks was measured. …After 6 hours of incubation with erythritol, the amount of hydrogen produced by fecal microbiota was comparable to that in the control flask, but the amount of hydrogen produced in the glucose and lactitol flasks was significantly higher than that in the control or erythritol flasks (p < 0.001).

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Biological Half-Life
The mean half-life of orally administered lactitol was 2.4 hours.

Protein Binding
Since lactitol is hardly absorbed systemically, it is unlikely to bind to proteins. Non-Human Toxicity Values Rat Dermal LD50: >4,500 mg/kg body weight Rat Oral LD50: >10,000 mg/kg body weight Rat Oral LD50: 30 g/kg Mouse Oral LD50: >23 g/kg

Lactitol or lactulose in the treatment of chronic constipation: result of a systematic. J Indian Med Assoc. 2010 Nov;108(11):789-92.

Therapeutic Uses
Sugar alcohols; laxatives; sweeteners
Lactitol (β-galactoside-sorbitol) has recently been compared with lactulose in some studies for the treatment of chronic hepatic encephalopathy, but the sample sizes in each study were small, and the results were controversial. We investigated the efficacy and tolerability of these two compounds through a meta-analysis based on published controlled trials. This study only included controlled or randomized trials involving patients with cirrhosis due to chronic hepatic encephalopathy. Parameters analyzed included the Conn portosystemic encephalopathy index after treatment, the proportion of patients with improvement, and the proportion of patients experiencing treatment-related adverse reactions (flatulence, diarrhea). A literature search revealed five studies comparing the efficacy of lactitol and lactulose in chronic hepatic encephalopathy. Four of these were crossover studies, including 48 patients; one was a parallel study, including 29 patients. Treatment duration ranged from 3 to 6 months. All studies found similar efficacy between the two drugs. However, some differences were observed in the relative incidence of adverse reactions (flatulence). Meta-analysis showed no statistically significant difference in the porta body encephalopathy index after treatment with lactitol or lactulose. The proportion of patients improving after treatment with either lactitol or lactulose was similar. Conversely, the analysis showed a higher incidence of flatulence in the lactulose treatment group compared to the lactitol group (p<0.01). In conclusion, this meta-analysis indicates no statistically significant difference in the therapeutic effects of lactitol and lactulose, but a higher incidence of flatulence in the lactulose group. This suggests that lactitol should be superior to lactulose in the treatment of chronic hepatic encephalopathy. Preliminary data suggest that lactitol (β-galactoside-sorbitol), a novel synthetic non-absorbable disaccharide, has beneficial effects on chronic porta body encephalopathy. To compare the efficacy of lactitol and lactulose in treating acute portal encephalopathy (PSE), 40 patients with acute exacerbations of cirrhosis were randomly assigned to two groups: Group A (n=20) received lactulose (30 mL/6 hr), and Group B (n=20) received lactitol (12 g/6 hr). Dosage was adjusted daily to achieve twice-daily bowel movements. Treatment lasted for 5 days. The two groups were similar in age, sex, liver and kidney function, precipitating factors, and the severity of PSE assessed by clinical examination, electroencephalography, and digit-connection test. Complete remission of PSE symptoms was achieved in 11 patients from each group. During the study period, moderate improvement in PSE symptoms was observed in 5 patients in the lactulose group and 6 patients in the lactitol group. Ultimately, 4 patients in the lactulose group and 3 patients in the lactitol group were unresponsive to treatment. No treatment-related side effects were observed in either group. These results suggest that lactitol is comparable to lactulose in treating patients with cirrhosis and acute PSE.

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Pharmacodynamics
Lactitol promotes intestinal motility by absorbing water in the gastrointestinal tract. Oral lactitol may reduce the absorption of concomitant medications—other oral medications should be taken at least 2 hours before or at least 2 hours after taking lactitol.

C12H24O11

344.31

344.131

C, 41.86; H, 7.03; O, 51.11

585-86-4

Lactitol monohydrate;81025-04-9

157355

Crystals from absolute ethanol

1.7±0.1 g/cm3

788.5±60.0 °C at 760 mmHg

98-102ºC

430.7±32.9 °C

0.0±6.2 mmHg at 25°C

1.634

-5.14

9

11

8

23

343

9

OC[C@@H]([C@H]([C@H](O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)[C@@H](CO)O)O)O

VQHSOMBJVWLPSR-JVCRWLNRSA-N

InChI=1S/C12H24O11/c13-1-4(16)7(18)11(5(17)2-14)23-12-10(21)9(20)8(19)6(3-15)22-12/h4-21H,1-3H2/t4-,5+,6+,7+,8-,9-,10+,11+,12-/m0/s1

(2S,3R,4R,5R)-4-(((2S,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)hexane-1,2,3,5,6-pentaol

Lactitol; Lactit; Lactosit Miruhen; NSC 231323; NSC-231323; NSC231323;

2934.99.03.00

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~68 mg/mL ( ~197.49 mM)

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.)