Absorption, Distribution and Excretion
In uremic patients, approximately 7% of ingested mannitol is absorbed during gastrointestinal instillation. Following inhalation of 635 mg mannitol powder, the peak plasma concentration (Cmax) reaches 13.71 μg/mL (Tmax) within 1.5 hours, with a mean systemic AUC of 73.15 μg·h/mL. Mannitol is primarily excreted unchanged in the urine. In healthy volunteers, after oral inhalation of 635 mg mannitol, 55% of the total dose was excreted unchanged in the urine; after oral or intravenous administration of 500 mg mannitol, the corresponding absorption rates were 54% and 87%, respectively. The volume of distribution for intravenously administered mannitol is 34.3 L. The total clearance of intravenously administered mannitol is 5.1 L/hr, and the renal clearance is 4.4 L/hr. Mannitol is generally considered not to be absorbed from the gastrointestinal tract. However, recent studies contradict this view, as 18% of orally administered D-(14)C mannitol was recovered in the urine of human subjects within 48 hours without change; within 12 hours, up to 19% of mannitol was present in exhaled air as carbon dioxide. 32% of the unabsorbed substance was found in feces within 48 hours. The apparent volume of distribution of certain substances (such as mannitol) corresponds to the total extracellular fluid (approximately 20% of body weight), and they can penetrate capillary membranes but not cell membranes. Mannitol has an extremely low reabsorption rate, and in many practical applications, the renal tubules can be considered impermeable to it. …Osmotic diuretics, as the name suggests, have a very low reabsorption rate in the renal tubules and therefore cannot be absorbed from the gastrointestinal tract. …These drugs must be administered via the parenteral route… to achieve effective plasma concentrations. Mannitol is hardly metabolized to glycogen in the liver.
...Polyhydroxy sugar alcohols...Mannitol (C6H14O6)...is mainly excreted unchanged in the urine.
Mannitol is abundant in Aspergillus oryzae spores and is rapidly metabolized in the early stages of germination. D-mannitol dehydrogenase converts it to fructose...
...After absorption from the digestive tract, the metabolic pathway of mannitol in animals (monkeys, rabbits, rats, dogs, etc.) includes: a small amount is converted into glycogen in the liver, and the remainder is excreted unchanged in the urine.

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Biological half-life
The elimination half-life of orally administered mannitol is 4.7 hours; the mean terminal elimination half-life is similar regardless of the route of administration (oral, inhalation, and intravenous).

Interactions
Hydroxyurea (HU) is a potent mammalian teratogen. Within 2-4 hours of maternal injection, HU causes: 1) rapid embryonic cell death; 2) significant inhibition of embryonic DNA synthesis. Various antioxidants can delay embryonic cell death and reduce the incidence of birth defects. Antioxidants do not block the inhibition of DNA synthesis, suggesting that early embryonic cell death is not caused by DNA synthesis inhibition. We hypothesize that certain HU molecules may react within the embryo, generating H₂O₂ and subsequent free radicals, including highly reactive hydroxyl radicals. These free radicals may lead to early cell death; antioxidants are thought to terminate abnormal free radical reactions, thereby mitigating developmental toxicity. To investigate whether hydroxyl radicals cause early cell death, researchers subcutaneously injected pregnant New Zealand white rabbits with a teratogenic dose of hydroxyurea (HU, 650 mg/kg) on day 12 of gestation, with or without the addition of 550 mg/kg of D-mannitol (Man, a hydroxyl radical-specific scavenger). Rabbits in the osmolarity control group were injected with HU, along with 550 mg/kg of xylose (Xyl, an inactive aldose). At full term, Man (HU) mitigated the teratogenic effects of HU, manifested as a reduced incidence of expected limb deformities. Xyl had no significant effect on the teratogenic effects of HU. Histological examination of limb buds in female rabbits 3-8 hours after injection revealed that Man delayed HU-induced cell death by up to 4 hours. Xyl had no such effect. To demonstrate the role of mannitol (Man) in the embryo, researchers administered intraperitoneal injections (mannitol, xylitol, or saline) at different implantation sites, followed by subcutaneous injections of hydroxyurea (HU) into pregnant ewes. Embryos were retrieved 3-8 hours later. The limb buds of embryos injected with saline and xylitol showed a typical pattern of widespread HU-induced cell death within 3-4 hours, while the embryos injected with mannitol showed cell death 5-8 hours later. These results are consistent with reports of antioxidant-mediated mitigation of HU-induced developmental toxicity and the hypothesis that hydroxyl radicals are the main active substances in HU-induced early embryonic cell death. ...Pentobarbital can alleviate blood-brain barrier disruption induced by hypertonic mannitol. This may be at least partly attributed to the hypotensive effect of pentobarbital. Significance: When the blood-brain barrier (BBB) is disrupted by hypertonic solutions, pentobarbital can reduce the degree of BBB leakage. The systemic hypotension induced by pentobarbital plays an important role in reducing leakage. Our study suggests that pentobarbital may effectively protect the BBB when it is disrupted. Furthermore, systemic blood pressure plays a crucial role in determining the degree of BBB disruption.

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Non-human toxicity values
Oral LD50 in rats: 13,500 mg/kg
Intravenous LD50 in rats: 9690 mg/kg
Oral LD50 in mice: 22 g/kg
Intraperitoneal LD50 in mice: 14 g/kg
Intravenous LD50 in mice: 7470 mg/kg

[1]. The mannitol operon repressor MtlR belongs to a new class of transcription regulators in bacteria. J Biol Chem, 2009. 284(52): p. 36670-9.

[2]. Mannitol lowers fat digestibility and body fat accumulation in both normal and cecectomized rats. J Nutr Sci Vitaminol (Tokyo), 2009. 55(3): p. 242-51.

[3]. Hanieh, H. and E. Sakaguchi, Effect of D-mannitol on feed digestion and cecotrophic system in rabbits. Anim Sci J, 2009. 80(2): p. 157-62.

[4]. Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg. 1992;77(4):584-589.

[5]. Sakaguchi E. Mannitol improves absorption and retention of calcium and magnesium in growing rats. Nutrition. 2013;29(1):325-331.

[6]. Multiple-dose mannitol reduces brain water content in a rat model of cortical infarction. Stroke. 1997;28(7):1437-1444.

[7]. D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism. Cells. 2021;10(4):768. Published 2021 Mar 31.

Therapeutic Uses
Osmotic Diuretic
Medication (Veterinary): Pretreatment with a 10% mannitol solution before aortic angiography can protect the kidneys and reduce the incidence of paraplegia and azotemia in dogs.
Medication (Veterinary): Used in dogs as an osmotic diuretic to induce cellular dehydration, thereby reducing intraocular pressure in patients with glaucoma and alleviating cerebral edema after surgery or injury.
Dosage for reducing intracranial pressure and brain volume before neurosurgery, or for reducing intraocular pressure… For the treatment of congestive glaucoma or ophthalmic surgery, the dosage is 1.5 to 2 g/kg, administered intravenously over 30 to 60 minutes in a 15% or 20% solution.
For more complete data on the therapeutic uses of D-mannitol (15 in total), please visit the HSDB record page.

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Drug Warnings
In edematous conditions with decreased cardiac reserve, the risks of using mannitol may far outweigh any therapeutic benefits.
Contraindications for mannitol include kidney disease, anuria, significant pulmonary congestion or edema, significant dehydration, and intracranial hemorrhage. Bleeding…Mannitol should be discontinued if the patient develops progressive renal impairment, heart failure, or pulmonary congestion.
The safety of mannitol in pregnancy and children under 12 years of age has not been established.
Artificial hypophosphatemia was observed in one patient who received a high-dose intravenous injection of mannitol. Concentrations as low as 25 mmol/L can inhibit the DuPont ACA endpoint assay for phosphorus; kinetics are unaffected. The mannitol interference mechanism is binding to molybdate, leading to a decreased colorimetric rate and a delay in endpoint measurement.
For more complete data on drug warnings for D-mannitol (9 of 9), please visit the HSDB record page.

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Pharmacodynamics
From a chemical perspective, mannitol is an alcohol and sugar, or polyol; it is similar to xylitol or sorbitol. However, mannitol readily loses hydrogen ions in aqueous solutions, making the solution acidic. Therefore, substances such as sodium bicarbonate are usually added to adjust its pH. Mannitol is commonly used to increase urine output (diuretics). It is also used to treat or prevent conditions caused by increased body fluid/water (e.g., cerebral edema, glaucoma, kidney failure). Mannitol is often used in combination with other diuretics (e.g., furosemide, chlorothiazide) and/or intravenous infusions. Inhalation of mannitol may cause bronchospasm and hemoptysis; if any of these occur, inhalation of mannitol should be stopped immediately.

C6H14O6

182.1718

182.079

69-65-8

D-Mannitol-d8;D-Mannitol-13C;132202-29-0;D-Mannitol-13C6;287112-34-9;D-Mannitol-2-13C;287100-69-0;D-Mannitol-d2;2649096-16-0;D-Mannitol-d;75607-68-0;D-Mannitol-13C,d2;1217463-58-5

6251

White to off-white solid powder

1.6±0.1 g/cm3

494.9±0.0 °C at 760 mmHg

167-170ºC

292.5±23.3 °C

0.0±2.8 mmHg at 25°C

1.597

-4.67

121.38

6

6

5

12

105

4

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

FBPFZTCFMRRESA-KVTDHHQDSA-N

InChI=1S/C6H14O6/c7-1-3(9)5(11)6(12)4(10)2-8/h3-12H,1-2H2/t3-,4-,5-,6-/m1/s1

(2R,3R,4R,5R)-hexane-1,2,3,4,5,6-hexol

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 : ≥ 36 mg/mL (~197.62 mM)

配方 1 中的溶解度: 100 mg/mL (548.94 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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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。