Absorption, Distribution and Excretion
In muscle and nerve, most of the creatine is phosphorylated to phosphocreatine (pCr) in a reaction that is catalyzed by the enezyme creatine kinase (CK), there are three isoforms of (isoenzymes) of CK. CK-MM is the skeletal muscle isoform; CK-BB, the brain isoform, and CK-MB, the isoform found in cardiac muscle. Most of the PCr in the body is in skeletal muscle.
Creatine is absorbed from the small intestines and enters the portal circulation and is transported to the liver. The ingested creatine, and the creatine made in the liver, is then transported into the systemic circulation and distributed into various tissues of the body, including muscle and nerves, by crossing the cell membrane via a specific creatine-transported system against a 200:1 gradient.

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Metabolism / Metabolites
Within muscle and nerve cells, about 60 to 67% of the creatine entering the cells gets converted to phosphocreatine via the enzyme creatine kinase. About 2% of creatine is converted to creatinine, and both creatine and creatinine are excreted by the kidneys.

Half Life: 3 hours

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Biological Half-Life
3 hours

Toxicity Summary
In the muscles, a fraction of the total creatine binds to phosphate - forming creatine phosphate. The reaction is catalysed by creatine kinase, and the result is phosphocreatine (PCr). Phosphocreatine binds with adenosine diphosphate to convert it back to ATP (adenosine triphosphate), an important cellular energy source for short term ATP needs prior to oxidative phosphorylation.

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Creatine is used as a dietary supplement to increase muscle mass and improve exercise performance. Creatine is a normal component of human milk, supplying about 9% of the infant’s daily requirements. Milk levels of creatine have not been measured after exogenous administration in humans. Creatine is converted into creatinine in the mother's and infant's bodies. It may increase the infant's serum creatinine, which may alter estimations of the infant's kidney function. Some authors speculate that creatine supplementation of nursing mothers might help avoid creatine deficiency syndromes, but no studies are available that test this hypothesis. Until more data are available, it is probably best to avoid creatine supplementation unless it is prescribed by a healthcare professional.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

Creatine is a glycine derivative having methyl and amidino groups attached to the nitrogen. It has a role as a neuroprotective agent, a nutraceutical, a human metabolite, a mouse metabolite and a geroprotector. It is a member of guanidines and a glycine derivative. It is a conjugate acid of a creatinate. It is a tautomer of a creatine zwitterion.
An amino acid derivative that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine.
Creatine has been reported in Glycine max, Citrus reticulata, and other organisms with data available.
Creatine is an endogenous amino acid derivative produced by vertebrate animals and occurring primarily in muscle cells. Creatine is important for energy storage; it is phosphorylated to creatine phosphate, which serves as a phosphate donor in the conversion of ADP to ATP and supplies energy necessary for muscle contraction. Dietary supplementation with creatine may improve muscle wasting associated with cancer and other chronic diseases.
Creatine is an amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. Creatine functions as part of the cell's energy shuttle. The high energy phosphate group of ATP is transferred to creatine to form phosphocreatine in the following reaction: Cr + ATP <-> PCr + ADP. This reaction is reversibly catalyzed by creatine kinase. In the human body creatine is synthesized mainly in the liver by the use of parts from three different amino acids - arginine, glycine, and methionine. 95% of it is later stored in the skeletal muscles, with the rest in the brain, heart, testes.
An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as CREATININE in the urine.

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Drug Indication
For nutritional supplementation, also for treating dietary shortage or imbalance.

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Mechanism of Action
In the muscles, a fraction of the total creatine binds to phosphate - forming creatine phosphate. The reaction is catalysed by creatine kinase, and the result is phosphocreatine (PCr). Phosphocreatine binds with adenosine diphosphate to convert it back to ATP (adenosine triphosphate), an important cellular energy source for short term ATP needs prior to oxidative phosphorylation.
Supplemental creatine may have an energy-generating action during anaerobic exercise and may also have neuroprotective and cardioprotective actions.
Creatine, creatine kinase and phosphocreatine make up an intricate cellular enegy buffering and transport system connecting sites of energy production in the mitochondria with sites of energy consumption. CK is a key enzyme in involved in cellular energy homeostasis. It reversibly catalyzes the transfer of the high-energy phosphate bond in PCr to adenosine diphosphate (ADP) to form adenosine triphosphate (ATP), and it catalyzes the transfer of the high-energy phosphate bond in ATP to creatine to form PCr. During periods of intense exercise and skeletal muscle contraction, bioenergetic metabolism switches from one in which oxidative phosphorylation is the major pathway of ATP production to one in which so-called anaerobic glycolysis becomes dominant.

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Therapeutic Uses
Creatine, as well as a creatine analogue called cyclocreatine, inhibit growth of a broad range of solid tumors in rat models of cancer; these tumors express high levels of CK. Although the mechanism for tumor inhibition is unknown...

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Drug Warnings
Phosphocreatine inhibits enzymes in the glycolitic pathway, including glyceraldehydes-3-phosphate dehydrogenase, phosphofructokinase and pyruvate kinase.
Safety data are lacking and are urgently needed, especially for long-term use of creatine and for use among the pediatric population (including adolescence) and among those in poor health. There are some reports that long-term use of creatine may be nephrotoxic. This needs further investigation before long-term creatine supplementation can be recommended under any circumstance.
Creatine is contraindicated in those with renal failure and renal disorders such as nephritic syndrome.
Anecdotal reports of adverse events to FDA have included rash, dyspnea, vomiting, diarrhea, nervousness, anxiety, migraine, fatigue, polymyositis, myopathy,seizures and atrial fibrillation.
There are reports of elevated serum creatinine, a metabolite of creatine and a marker of kidney function, in some who take creatine and have normal renal function. This /effect on renal function tests/ is reversible upon discontinuation of creatine.

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Pharmacodynamics
Creatine is a essential, non-proteinaceous amino acid derivative found in all animals. It is synthesized in the kidney, liver, and pancreas from L-arginine, glycine and L-methionine. Following its biosynthesis, creatine is transported to the skeletal muscle, heart, brain and other tissues. Most of the creatine is metabolized in these tissues to phosphocreatine (creatine phosphate). Phosphocreatine is a major energy storage form in the body. Supplemental creatine may have an energy-generating action during anaerobic exercise and may also have neuroprotective and cardioprotective actions.

C4H9N3O2

131.14

131.069

57-00-1

586

White to off-white solid powder

1.4±0.1 g/cm3

271.6±42.0 °C at 760 mmHg

~295 °C (dec.)

118.1±27.9 °C

0.0±1.2 mmHg at 25°C

1.552

-1.88

3

3

3

9

134

0

O([H])C(C([H])([H])N(/C(=N/[H])/N([H])[H])C([H])([H])[H])=O

CVSVTCORWBXHQV-UHFFFAOYSA-N

InChI=1S/C4H9N3O2/c1-7(4(5)6)2-3(8)9/h2H2,1H3,(H3,5,6)(H,8,9)

2-[carbamimidoyl(methyl)amino]acetic acid

NSC-8752; NSC 8752; Creatine

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 : ~6.25 mg/mL (~47.66 mM)

Solubility in Formulation 1: 20 mg/mL (152.51 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

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