Absorption, Distribution and Excretion
Magnesium is excreted solely by the kidney at a rate proportional to the serum concentration and glomerular filtration.
Magnesium sulfate is excreted by the kidneys at a rate that varies from one patient to another but that is directly proportional to the serum concn and glomerular filtration.
PLASMA CONCN OF MAGNESIUM INCR IN FETUS & APPROACH MATERNAL BLOOD VALUES AFTER MAGNESIUM SULFATE ADMIN IN ECLAMPSIA & PREECLAMPSIA.

---

Metabolism / Metabolites
None
Magnesium is almost exclusively excreted in the urine, with 90% of the dose excreted during the first 24 hours after an intravenous infusion of MgSO4. The pharmacokinetic profile of MgSO4 after intravenous administration can be described by a 2-compartment model with a rapid distribution (a) phase, followed by a relative slow beta phase of elimination.
Route of Elimination: Magnesium is excreted solely by the kidney at a rate proportional to the serum concentration and glomerular filtration.
Half Life: 43.2 hours (for newborns)

---

Biological Half-Life
43.2 hours (for newborns)

Toxicity Summary
Magnesium is the second most plentiful cation of the intracellular fluids. It is essential for the activity of many enzyme systems and plays an important role with regard to neurochemical transmission and muscular excitability. Magnesium sulfate reduces striated muscle contractions and blocks peripheral neuromuscular transmission by reducing acetylcholine release at the myoneural junction. Additionally, Magnesium inhibits Ca²⁺ influx through dihydropyridine-sensitive, voltage-dependent channels. This accounts for much of its relaxant action on vascular smooth muscle.

---

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Intravenous magnesium increases milk magnesium concentrations only slightly and oral absorption of magnesium by the infant is poor, so maternal magnesium therapy is not expected to affect the breastfed infant's serum magnesium. Although intravenous magnesium sulfate given prior to delivery might affect the infant's ability to breastfeed, intention to breastfeed may be a more important determinant of breastfeeding initiation. Postpartum use of intravenous magnesium sulfate for longer than 6 hours appears to delay the onset of lactation. One group of experts recommends reserving postpartum magnesium sulfate prophylaxis for those women with persistent neurologic symptoms within 7 days of birth.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
One mother who received intravenous magnesium sulfate for 3 days for pregnancy-induced hypertension had lactogenesis II delayed until day 10 postpartum. No other specific cause was found for the delay, although a complete work-up was not done. A subsequent controlled clinical trial found no evidence of delayed lactation in mothers who received intravenous magnesium sulfate therapy. Some, but not all, studies have found a trend toward increased time to the first feeding or decreased sucking in infants of mothers treated with intravenous magnesium sulfate during labor because of placental transfer of magnesium to the fetus. Another study found that among women with severe pre-eclampsia who received intravenous magnesium sulfate for up to one day postpartum and who intended to breastfeed, 85% of infants receiving routine well-baby care and 69% of those admitted to the NICU, breastfeeding was successfully initiated.
A study randomized women with preeclampsia to receive intravenous magnesium sulfate for either 6 or 24 hours postpartum. There was no difference in the rate of eclampsia between the two groups. However, those who received the infusion for 24 hours had a delayed onset of lactation, 36.5 hours compared with 25.7 hours in the 6-hour group.
A prospective, multicenter, randomized, controlled trial in 9 Latin American maternity hospitals compared patients with severe pre-eclampsia who had received at least 8 grams of magnesium sulfate prior to placebo. Patients were randomized to continue magnesium sulfate for 24 hours postpartum (n = 555) or stopping the infusion (n = 558). The time to lactation was significantly delayed in those who received magnesium sulfate postpartum (24.1 vs. 17.1 hours).
A study randomized pregnant women with moderate to severe pre-eclampsia to receive magnesium sulfate intravenously infused at the same dose (not specified) for 8 or 24 hours. In patients who received the 8-hour infusion, the mean time to initiate breastfeeding was 14.6 hours compared to 24.3 hours in the patients who received the 24-hour infusion, which was a statistically significant difference.
A retrospective chart review of mothers who delivered at the University of Chicago found that intravenous magnesium sulfate during delivery was associated with over 60% reduced odds of breastfeeding initiation compared to mothers who received no magnesium.

---

Protein Binding
25-30%

---

Toxicity Data
LD50: 1200 mg/kg (rat, parenteral-subcutaneous).
The first warning of impending toxicity is loss of the patellar reflex at plasma concentrations between 3.5 and 5 mmol/L. Respiratory paralysis occurs at 5 to 6.5 mmol/L. Cardiac conduction is altered at greater than 7.5 mmol/L, and cardiac arrest can be expected when concentrations of magnesium exceed 12.5 mmol/L.

---

Interactions
ADMIN OF MAGNESIUM SULFATE IN PREECLAMPSIA & ECLAMPSIA POTENTIATES NEUROMUSCULAR BLOCKADE PRODUCED BY D-TUBOCURARINE, DECAMETHONIUM, & SUCCINYLCHOLINE.
When barbiturates, opiates, general anesthetics, or other CNS depressants are administered concomitantly with magnesium sulfate, dosage of these agents must be carefully adjusted because of the additive central depressant effects.
...Magnesium inhibited extracellular calcium entry, intracellular calcium release, cytosolic calcium oscillations, and phasic contractions of myometrial smooth muscle /induced by oxytocin and other uterotonic agonists/.
...The present in vivo rat study examined the effect of magnesium sulfate to alter the pressor response to norepinephrine (NE) and angiotensin II (A II). Magnesium doses were chosen to approximate those used in treating preeclampsia. NE resulted in a significant rise in mean arterial pressure (delta MAP, 46 +/- 3.7 mmHg; p<0.001). A II also resulted in a significant rise in MAP (delta MAP, 23 +/- 3.6 mmHg, p<0.02). Magnesium sulfate alone had no significant effect on MAP but attenuated the pressor response to both NE (delta MAP, 16 +/- 1.5 mmHg) and A II (delta MAP, 12 +/- 2.5 mmHg). After discontinuation of the magnesium sulfate infusion, the control pressor responses to NE and A II were again seen (delta MAP, 39 +/- 3.5 mmHg and delta MAP, 28 +/- 4.2 mmHg, respectively). Although magnesium sulfate is not a primary antihypertensive agent, it may have effects on blood pressure by attenuating the actions of circulating vasoconstrictors.
For more Interactions (Complete) data for MAGNESIUM SULFATE (6 total), please visit the HSDB record page.

---

Non-Human Toxicity Values
LD50 Mouse subcutaneous 645 mg/kg
LD50 Rat subcutaneous 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; Anti-Arrhythmia Agents; Anticonvulsants; Calcium Channel Blockers; Cathartics; Tocolytic Agents
AN EFFECTIVE & WIDELY EMPLOYED SALINE CATHARTIC. /HEPTAHYDRATE, USP/
FULL DOSES OF SALINE CATHARTICS (15 G MAGNESIUM SULFATE OR ITS EQUIVALENT) PRODUCE A SEMIFLUID OR WATERY EVACUATION IN 3 HR OR LESS. LOW DOSES PRODUCE A LAXATIVE EFFECT WITH GREATER LATENCY.
A COLD, WET COMPRESS OF MAGNESIUM SULFATE SOLN IN WATER HAS BEEN EMPLOYED IN TREATMENT OF SUCH SKIN DISORDERS AS ERYSIPELAS. HOT CONCN AQ SOLN...(ABOUT 1 LB/PINT OF WATER) ARE SOMETIMES USED IN TREATMENT OF DEEP-SEATED INFECTIONS, CLOTHS BEING SATURATED & APPLIED WHILE HOT. ACTION MUCH LIKE THAT OF POULTICE. /HEPTAHYDRATE/
For more Therapeutic Uses (Complete) data for MAGNESIUM SULFATE (32 total), please visit the HSDB record page.

---

Drug Warnings
SOME ABSORPTION OF COMPONENT IONS OF SALINE CATHARTICS DOES OCCUR, & IN CERTAIN INSTANCES THEY MAY PRODUCE SYSTEMIC TOXICITY. IN AN INDIVIDUAL WITH IMPAIRED RENAL FUNCTION, ACCUM OF MAGNESIUM IONS IN BODY FLUIDS MAY BE SUFFICIENT TO CAUSE INTOXICATION. MAGNESIUM CATHARTICS SHOULD BE ADMIN ONLY IF RENAL FUNCTION IS ADEQUATE.
THE DRUG IS GENERALLY SAFE BUT CAN CAUSE TEMPORARY LOSS OF DEEP TENDON REFLEXES IN MOTHER & MAY SUPPRESS SKELETAL MUSCLE ACTIVITY IN NEONATE. IT SHOULD NOT BE USED IN PT WITH HEART DISEASE...
NEONATE MAY BE DROWSY & EXHIBIT RESP DIFFICULTIES & DIMINISHED MUSCLE TONE. HOWEVER...NO RELATIONSHIP BETWEEN PLASMA MAGNESIUM CONCN OF BLOOD COLLECTED FROM UMBILICAL CORD & THE APGAR SCORE /HAS BEEN FOUND/.
Patients receiving parenteral magnesium sulfate shold be observed carefully, and serum magnesium concn should be monitored to avoid overdosage. ... An IV preparation of a calcium salt (e.g., calcium gluconate) should be readily available for use when magnesium sulfate is given IV. /Magnesium sulfate injection/
For more Drug Warnings (Complete) data for MAGNESIUM SULFATE (14 total), please visit the HSDB record page.

---

Pharmacodynamics
Magnesium sulfate is a small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. Magnesium sulfate is gaining popularity as an initial treatment in the management of various dysrhythmias, particularly torsades de pointes, and dyrhythmias secondary to TCA 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.

---

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).

View More

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)

---

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).

View More

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

---

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.

---

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