Absorption, Distribution and Excretion
Magnesium is completely excreted via the kidneys, with the excretion rate proportional to serum concentration and glomerular filtration rate (GFR). Magnesium sulfate is also excreted via the kidneys, with the excretion rate varying from person to person but proportional to serum concentration and GFR. In patients with eclampsia and preeclampsia, fetal plasma magnesium concentrations increase after magnesium sulfate treatment, approaching maternal serum magnesium levels. Metabolism/Metabolites None Magnesium is almost entirely excreted in the urine; after intravenous infusion of magnesium sulfate, 90% of the dose is excreted within the first 24 hours. The pharmacokinetic characteristics of intravenously administered magnesium sulfate can be described using a two-compartment model, which includes a rapid distribution (a) phase and a relatively slow elimination (β) phase. Elimination Pathway: Magnesium is excreted solely via the kidneys, with the excretion rate proportional to serum concentration and GFR.
Half-life: 43.2 hours (newborn)

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Biological half-life
43.2 hours (newborn)

Toxicity Summary
Magnesium is the second most abundant cation in intracellular fluid. It is essential for the activity of many enzyme systems and plays a significant role in neurochemical transmission and muscle excitability. Magnesium sulfate reduces skeletal muscle contraction and blocks peripheral neuromuscular transmission by decreasing acetylcholine release at neuromuscular junctions. Furthermore, magnesium inhibits the influx of Ca²⁺ through dihydropyridine-sensitive voltage-dependent channels. This explains most of its relaxing effect on vascular smooth muscle. Effects During Pregnancy and Lactation ◉ Overview of Use During Lactation Intravenous magnesium administration only slightly increases the concentration of magnesium in breast milk, and the absorption rate of orally administered magnesium by infants is very low; therefore, maternal magnesium treatment is not expected to affect serum magnesium levels in breastfed infants. Although antepartum intravenous magnesium sulfate administration may affect an infant's ability to breastfeed, the willingness to breastfeed is likely a more significant determinant of initiation of breastfeeding. Postpartum intravenous magnesium sulfate administration more than 6 hours after delivery appears to delay the onset of lactation. A group of experts recommends considering postpartum magnesium sulfate prophylactic treatment for women with persistent neurological symptoms within 7 days postpartum.
◉ Effects on breastfed infants
As of the revision date, no relevant published information was found.
◉ Effects on lactation and breast milk
A mother who received 3 days of intravenous magnesium sulfate for gestational hypertension experienced delayed lactation stage II until 10 days postpartum. Although no comprehensive examination was conducted, no other specific cause for the delay was found. A subsequent controlled clinical trial found no evidence of delayed lactation in mothers receiving intravenous magnesium sulfate. Some studies (but not all) have found that infants born to mothers who received intravenous magnesium sulfate during delivery tend to have longer first feeding times or shorter suckling times due to placental transfer of magnesium to the fetus. Another study found that among patients with severe preeclampsia who received intravenous magnesium sulfate for up to one day postpartum, 85% of infants receiving routine infant care and 69% of infants admitted to the neonatal intensive care unit (NICU) successfully started breastfeeding.
One study randomized patients with preeclampsia to two groups, receiving intravenous magnesium sulfate for 6 hours or 24 hours postpartum. There was no difference in the incidence of preeclampsia between the two groups. However, patients receiving the 24-hour infusion had a later onset of lactation, at 36.5 hours, compared to 25.7 hours in the 6-hour group.
A prospective, multicenter, randomized controlled trial conducted at nine maternity hospitals in Latin America compared patients with severe preeclampsia who received at least 8 grams of magnesium sulfate prenatally with those who received a placebo. Patients were randomized to either continue magnesium sulfate infusion for 24 hours postpartum (n = 555) or discontinue infusion (n = 558). Patients continuing magnesium sulfate infusion postpartum had a significantly delayed onset of lactation (24.1 hours vs. 17.1 hours).
One study randomized pregnant women with moderate to severe preeclampsia to receive the same dose (unspecified) of magnesium sulfate intravenously for 8 hours or 24 hours. Patients receiving an 8-hour infusion had a statistically significant time to breastfeeding initiation, averaging 14.6 hours, compared to 24.3 hours for those receiving a 24-hour infusion. A retrospective analysis of medical records from mothers who delivered at the University of Chicago found that intravenous magnesium sulfate during delivery reduced the likelihood of breastfeeding initiation by more than 60% compared to mothers who did not receive magnesium sulfate. Protein binding rate: 25-30%. Toxicity data: LD50: 1200 mg/kg (rat, parenteral-subcutaneous injection). The first warning sign of impending toxicity is loss of knee reflexes at plasma concentrations between 3.5 and 5 mmol/L. Respiratory paralysis occurs at concentrations between 5 and 6.5 mmol/L. Cardiac conduction changes occur at magnesium concentrations above 7.5 mmol/L; cardiac arrest may occur at concentrations exceeding 12.5 mmol/L.

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Interactions
Magnesium sulfate use in preeclampsia and eclampsia can enhance the neuromuscular blocking effects induced by D-tubocurarine, decanterium, and succinylcholine.
When barbiturates, opioids, general anesthetics, or other central nervous system depressants are used concomitantly with magnesium sulfate, the dosage of these drugs must be carefully adjusted due to the additive central depressant effects.
…Magnesium inhibits extracellular calcium ion influx, intracellular calcium ion release, cytoplasmic calcium ion oscillations, and rhythmic contractions of uterine smooth muscle induced by oxytocin and other uterine contraction agents.
…This study investigated the effects of magnesium sulfate on the pressor response to norepinephrine (NE) and angiotensin II (A II) in an in vivo rat experiment. The magnesium dosage used in the experiment was similar to that used to treat preeclampsia. NE significantly increased mean arterial pressure (MAP) (ΔMAP, 46 ± 3.7 mmHg; p<0.001). AII also significantly increased MAP (ΔMAP, 23 ± 3.6 mmHg; p<0.02). Magnesium sulfate alone had no significant effect on MAP, but it attenuated the pressor response to NE (ΔMAP, 16 ± 1.5 mmHg) and AII (ΔMAP, 12 ± 2.5 mmHg). After discontinuation of magnesium sulfate infusion, control pressor responses to norepinephrine (NE) and angiotensin II (AII) were observed again (mean arterial pressure changes of 39 ± 3.5 mmHg and 28 ± 4.2 mmHg, respectively). Although magnesium sulfate is not a primary antihypertensive agent, it may affect blood pressure by attenuating the effects of circulatory vasoconstrictors.
For more complete data on interactions of magnesium sulfate (6 items in total), please visit the HSDB record page.

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Non-human toxicity values
Mouse subcutaneous LD50: 645 mg/kg
Rat subcutaneous LD50: 1200 mg/kg

[1]. Clinical pharmacokinetic properties of magnesium sulphate in women with pre-eclampsia and eclampsia. BJOG. 2016;123(3):356-366.

[2]. Magnesium sulfate as a tocolytic agent. Semin Perinatol. 2001;25(4):236-247.

Therapeutic Uses
Analgesics; Anesthetics; Antiarrhythmics; Anticonvulsants; Calcium Channel Blockers; Laxatives; Uterine Contraction Inhibitors. A potent and widely used saline laxative. /Magnesium Sulfate Heptahydrate, USP/ A sufficient dose of saline laxative (15 grams of magnesium sulfate or its equivalent) produces a semi-liquid or watery excretion within 3 hours or less. Lower doses produce a laxative effect, but with a slower onset. Cold compresses: Magnesium sulfate aqueous solution has been used to treat skin conditions such as erysipelas. Hot concentrated aqueous solutions (approximately 1 pound/pint of water) are sometimes used to treat deep infections; a cloth soaked in the solution is applied to the affected area while still warm. The effect is similar to a topical application. /Heptahydrate/ For more complete data on the therapeutic uses of magnesium sulfate (32 types), please visit the HSDB record page. Drug Warnings Some saline laxative components have ions that can be absorbed, potentially leading to systemic toxicity in certain situations. In patients with impaired renal function, the accumulation of magnesium ions in body fluids may be sufficient to cause poisoning. Magnesium laxatives should only be used when renal function is normal. This drug is generally safe, but may cause temporary loss of deep tendon reflexes in the mother and may inhibit skeletal muscle activity in the newborn. It is contraindicated in patients with heart disease. Newborns may experience lethargy, respiratory distress, and hypotonia. However… no association has been found between umbilical cord blood plasma magnesium concentration and Apgar score. Patients receiving parenteral magnesium sulfate should be closely monitored, and serum magnesium concentrations should be monitored to avoid overdose. …When administering magnesium sulfate intravenously, an intravenous preparation of calcium salts (e.g., calcium gluconate) should be available. /Magnesium Sulfate Injection/ For more complete data on drug warnings for magnesium sulfate (14 in total), please visit the HSDB record page.

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Pharmacodynamics
Magnesium sulfate is a colorless small crystal used as an anticonvulsant, laxative, and electrolyte supplement to treat preeclampsia and eclampsia. It directly inhibits the action potentials of uterine myocytes. Excitation and contraction become decoupled, leading to a decrease in contraction frequency and intensity. Magnesium sulfate is becoming increasingly popular as a primary treatment for various arrhythmias, especially torsades de pointes, as well as arrhythmias caused by tricyclic antidepressant overdose or digitalis toxicity.

MGO4S

120.3676

119.936

7487-88-9

10034-99-8 (heptahydrate)

24083

White to off-white solid powder

1.07 g/mL at 20 °C

330ºC at 760 mmHg

1124 °C

<0.1 mm Hg ( 20 °C)

0

4

0

6

62.2

0

CSNNHWWHGAXBCP-UHFFFAOYSA-L

InChI=1S/Mg.H2O4S/c;1-5(2,3)4/h;(H2,1,2,3,4)/q+2;/p-2

magnesium;sulfate

2934.99.9001

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, 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)

H2O: 25 mg/mL

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.)