Absorption, Distribution and Excretion
ITS ONSET OF ACTION BY ORAL ROUTE IS ABOUT 320 MIN...ITS DURATION OF ACTION BY THE ORAL ROUTE IS USUALLY SOMEWHAT LONGER AND ABSORPTION IS LESS ERRATIC THAN NEOSTIGMINE, WHICH ARE ADVANTAGES.
Plasma concn of pyridostigmine was determined in 2 nursing mothers who were receiving oral doses of pyridostigmine bromide, 120-300 mg daily. The drug was not detectable in infant plasma and there were no signs of drug effects in the infant.

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Metabolism / Metabolites
PYRIDOSTIGMINE AND ITS QUATERNARY ALCOHOL ARE...THE PREDOMINANT ENTITIES FOUND IN URINE AFTER ADMIN OF THIS DRUG TO MAN.

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Biological Half-Life
After admin of pyridostigmine bromide (200 nmol/kg, iv) to human subjects, the disposition half-life was 0.6-1.78 min and terminal half-life was 14.81-37.01 min. Clearance was 9.3-26.5 ml/min/kg which was greater than the presumptive value for glomerular filtration rate and the vol of distribution was 246.5-833.9 ml/kg.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because of the low levels of pyridostigmine in breastmilk, amounts ingested by the infant are small and infant serum levels are very low. Pyridostigmine is not expected to cause any adverse effects in breastfed infants. Most mothers with myasthenia gravis are able to nurse successfully with pyridostigmine treatment, but occasionally breastfeeding must be discontinued to avoid excessive fatigue in the mother.
◉ Effects in Breastfed Infants
A woman was taking pyridostigmine 120 mg every 4 to 5 hours for myasthenia gravis. Her breastfed (extent not stated) infant reportedly thrived and had no cholinergic side effects.
Two infants whose mothers were taking pyridostigmine 3 and 5 mg/kg daily during pregnancy and lactation were exclusively breastfed. Both infants gained weight and developed normally and had no signs of cholinergic side effects.
◉ Effects on Lactation and Breastmilk
Relevant published information in nursing mothers was not found as of the revision date. In animals, cholinergic drugs increase oxytocin release, and have variable effects on serum prolactin. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
In a case series of 69 pregnancies in 65 women with myasthenia gravis over 27 years, 49 patients received pyridostigmine during pregnancy and lactation. Lactation data were available for 33 patients, and 25 of them nursed successfully, although the number of these mothers who were taking pyridostigmine was not given. Nursing was sometimes disrupted to avoid exhaustion in the mother.

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Interactions
ACTIONS OF ANTICHOLINESTERASE AGENTS ON AUTONOMIC EFFECTOR CELLS & ON CORTICAL & SUBCORTICAL SITES IN CNS, WHERE RECEPTORS ARE LARGELY OF MUSCARINIC TYPE, ARE BLOCKED BY ATROPINE. /ANTI-CHE AGENTS/
A SINGLE CASE HAS BEEN REPORTED IN WHICH METHOCARBAMOL MAY HAVE IMPAIRED THE THERAPEUTIC EFFECT OF PYRIDOSTIGMINE BROMIDE IN A PATIENT WITH MYASTHENIA GRAVIS.
In anesthetized patients, pyridostigmine bromide mestinon 10 mg iv antagonized the neuromuscular block induced by d-tubocurarine chloride 0.29 mg/kg/hr. Adequate recovery from the neuromuscular block should be judged by the return of the twitch height to the control level & also by the restoration of well-sustained tetanus 30 cycles/sec to the level seen before d-tubocurarine chloride administration.
Prolonged effect of succinylcholine after neostigmine and pyridostigmine administration in patients with renal failure.
The amino acid gamma-aminobutyric acid (GABA), when given as supplement to pyridostigmine bromide reduced the incidence of malformations in chicken embryos.

Neuroscience.2013 Aug 29;246:391-6;Luminescence.2011 Nov-Dec;26(6):510-7.

Pyridostigmine bromide is a pyridinium salt.
Pyridostigmine is a drug that has been approved by the U.S. Food and Drug Administration (FDA) under the brand name Mestinon to treat a condition called myasthenia gravis and under the brand name Regonol to reverse the effects of muscle relaxants. In addition, pyridostigmine has been approved for use by military personnel as a pretreatment for exposure to the chemical nerve agent Soman. It is also being studied as an investigational drug to treat HIV infection.
As an investigational HIV drug, pyridostigmine belongs to a group of drugs called immune modulators. Immune modulators (also called immunomodulators) are substances that help to activate, boost, or restore normal immune function.
Researchers are currently studying whether pyridostigmine added to antiretroviral therapy (ART) can help a person with HIV increase their CD4 count.
Pyridostigmine Bromide is the bromide salt form of pyridostigmine, a quaternary ammonium carbamate derivative and a acetylcholinesterase inhibitor. Pyridostigmine bromide binds reversibly to acetylcholinesterase active sites in the peripheral nervous system, thereby preventing the breakdown of acetylcholine. This leads to an accumulation of acetylcholine at cholinergic synapses and facilitates transmission of impulses across the neuromuscular junction. Mediated through muscarinic receptors, this agent increases contraction of bronchial and intestinal smooth muscle and the exocrine glands secretions, while it causes paralysis of the skeletal muscles mediated through nicotinic receptors. In addition, pyridostigmine is used as a reversible blocking agent to prevent organophosphates from binding to the acetylcholinesterase receptors and thereby protect the nervous system from the effects of nerve agents such as Soman.
A cholinesterase inhibitor with a slightly longer duration of action than NEOSTIGMINE. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants.
See also: Pyridostigmine (has active moiety).

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Mechanism of Action
...PHARMACOLOGICAL EFFECTS OF ANTICHOLINESTERASE AGENTS ARE DUE PRIMARILY TO PREVENTION OF HYDROLYSIS OF /ACH/ ACETYLCHOLINE BY ACHE /ACETYLCHOLINESTERASE/ @ SITES OF CHOLINERGIC TRANSMISSION. TRANSMITTER THUS ACCUMULATES, AND THE ACTION OF ACH /ACETYLCHOLINE/ THAT IS LIBERATED BY CHOLINERGIC IMPULSES OR THAT LEAKS FROM THE NERVE ENDING IS ENHANCED.
Following admin of pyridostigmine bromide to rats, erythrocyte acetylcholinesterase activity recovered only slowly due to the covalent nature of inhibition. The logarithm of the plasma concn of pyridostigmine bromide was linearly related to the increase in tibialis twitch tension due to facilitation of neuromuscular transmission.
Of 12 analogs of pyridostigmine prepared by reacting 2-substituted 3-pyridinols with the desired carbamoyl chloride 2-iodo-3-(dimethylcarbamoyloxy)pyridine methiodide was the most active inhibitor of acetylcholinesterase and butyrylcholinesterase. The progressive inhibition curves for AChE and BuChE are compared and related to ionic attraction and steric requirements of the inhibitors.

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Therapeutic Uses
Cholinesterase Inhibitors; Parasympathomimetics
A QUATERNARY AMMONIUM ANTICHOLINESTERASE DRUG ...PRINCIPAL USE IS IN THE TREATMENT OF MYASTHENIA GRAVIS. ...
DOSAGE: THE EQUIVALENT PARENTERAL DOSE OF...PYRIDOSTIGMINE IS APPROX 1/30TH OF THE ORAL DOSE.
PYRIDOSTIGMINE HAS A SLOWER ONSET (13 MIN) THAN EDROPHONIUM (3 MIN) OR NEOSTIGMINE (6-8 MIN), BUT A LONGER DURATION OF ACTION THAN EITHER. FOR THIS REASON, IT HAS BEEN RECOMMENDED FOR PATIENTS WITH RENAL IMPAIRMENT.
For more Therapeutic Uses (Complete) data for PYRIDOSTIGMINE BROMIDE (9 total), please visit the HSDB record page.

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Drug Warnings
BROMIDE SENSITIVITY OCCASIONALLY OCCURS.
Maternal Medication usually Compatible with Breast-Feeding: Pyridostigmine: Reported Sign or Symptom in Infant or Effect on Lactation: None. /from Table 6/

C9H13BRN2O2

261.12

260.016

101-26-8

Pyridostigmine-d6 bromide;2375858-08-3;Pyridostigmine-d3 bromide

7550

White to off-white solid powder

0.9613 g/cm3 (20ºC)

88 (25 torr)

154 °C

1.48 (20ºC)

0

3

2

14

183

0

VNYBTNPBYXSMOO-UHFFFAOYSA-M

InChI=1S/C9H13N2O2.BrH/c1-10(2)9(12)13-8-5-4-6-11(3)7-8;/h4-7H,1-3H3;1H/q+1;/p-1

(1-methylpyridin-1-ium-3-yl) N,N-dimethylcarbamate;bromide

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 (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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (9.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (382.97 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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