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Clinical Pharmacology and Therapeutics May 1985Comparative pyridostigmine kinetics in plasma were measured in 10 healthy subjects given 4 mg iv and 60 mg oral pyridostigmine bromide. As determined from the AUC ratio,... (Comparative Study)
Comparative Study
Comparative pyridostigmine kinetics in plasma were measured in 10 healthy subjects given 4 mg iv and 60 mg oral pyridostigmine bromide. As determined from the AUC ratio, oral availability was 11.5% to 18.9% (means = 14.3%). Mean t 1/2 of the plasma level decline after oral dosing was 200 minutes, twice as long as the terminal elimination t1/2 after intravenous infusion (97 minutes). Thus absorption may proceed at a slower rate than elimination. Comparison of intraindividual data revealed strict dependence of the AUC on the infused dose (2, 4, and 8 mg) in one subject and variability in AUC up to a factor of two when two subjects took oral pyridostigmine three times. Patients with myasthenia who were receiving continuous therapy with oral pyridostigmine had AUC values per unit dose corresponding to those in healthy subjects. Storage stability of pyridostigmine in plasma required acidification of samples and storage at -75 degrees C. When native plasma was kept at -20 degrees C, there was appreciable loss of pyridostigmine within 1 to 2 months, the extent of which depended on the initial concentration.
Topics: Absorption; Administration, Oral; Adult; Aged; Chromatography, High Pressure Liquid; Drug Evaluation; Drug Storage; Female; Half-Life; Humans; Infusions, Parenteral; Kinetics; Male; Middle Aged; Myasthenia Gravis; Pyridostigmine Bromide
PubMed: 3987173
DOI: 10.1038/clpt.1985.78 -
The British Journal of Surgery May 2024Postoperative ileus, driven by the cholinergic anti-inflammatory pathway, is the most common complication in patients undergoing colorectal surgery. By inhibiting... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Postoperative ileus, driven by the cholinergic anti-inflammatory pathway, is the most common complication in patients undergoing colorectal surgery. By inhibiting acetylcholinesterase, pyridostigmine can potentially modulate the cholinergic anti-inflammatory pathway and accelerate gastrointestinal recovery. This study aimed to assess the efficacy of pyridostigmine in improving gastrointestinal recovery after colorectal surgery.
METHODS
This double-blinded RCT enrolled adult patients undergoing elective colorectal surgery at two hospitals in South Australia. Patients were randomized to 60 mg oral pyridostigmine or placebo twice daily starting 6 h after surgery until the first passage of stool. The primary outcome was GI-2, a validated composite measure of time to first stool and tolerance of oral diet. Secondary outcomes included incidence of postoperative ileus (defined as GI-2 greater than 4 days), duration of hospital stay, and 30-day complications, evaluated by intention-to-treat univariate analysis.
RESULTS
Of 130 patients recruited (mean(s.d.) age 58.4(16.4) years; 73 men, 56%), 65 were allocated to each arm. The median GI-2 was 1 day shorter with pyridostigmine compared with placebo (2 (i.q.r. 1-3) versus 3 (2-4) days; P = 0.015). However, there were no significant differences in postoperative ileus (17.2 versus 21.5%; P = 0.532) or duration of hospital stay (median 5 (i.q.r. 4-8.75) versus 5 (4-7.5) days; P = 0.921). Similarly, there were no significant differences in overall complications, anastomotic leak, cardiac complications, or patient-reported side effects.
CONCLUSION
Pyridostigmine resulted in a quicker return of GI-2 and was well tolerated. Larger multicentre studies are required to determine the optimal dosing and evaluate the impact of pyridostigmine in different surgical settings. Registration number: ACTRN12621000530820 (https://anzctr.org.au).
Topics: Humans; Male; Ileus; Female; Double-Blind Method; Middle Aged; Postoperative Complications; Cholinesterase Inhibitors; Pyridostigmine Bromide; Aged; Length of Stay; Adult; Treatment Outcome
PubMed: 38743864
DOI: 10.1093/bjs/znae121 -
British Journal of Clinical Pharmacology Oct 1982
Topics: Breast Feeding; Female; Humans; Milk, Human; Pyridostigmine Bromide; Time Factors
PubMed: 7138742
DOI: No ID Found -
Psychopharmacology Jul 2002Questions have been raised about the role pyridostigmine bromide (PB) plays in the etiology of Gulf War veterans' illnesses. There is a need to understand better the... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
RATIONALE
Questions have been raised about the role pyridostigmine bromide (PB) plays in the etiology of Gulf War veterans' illnesses. There is a need to understand better the physiological and behavioral effects of this drug, particularly at the 30-mg/8-h regimen recommended by the US Military. OBJECTIVE. To perform a double-blind, cross-over, dose-response study of PB in 67 healthy, young volunteers (31 women, 36 men).
METHODS
Volunteers were initially trained on a standardized test battery. Supervised administration of placebo (PL) and PB (every 8 h/5 days) occurred in each of two dosing weeks, separated by a non-dosing week. One group received 30 mg PB and PL, and the other 60 mg PB and PL. In each dosing week, the battery was performed after the first pill and again when steady-state plasma PB levels were achieved.
RESULTS
PB was associated with an overall improvement in reaction time on tests of memory and attention, and with a reduction in RMS error on a tracking task. PB slowed heart rate and decreased the high frequency component of heart rate variability (HF HRV). Dose-response effects were found only for HF HRV, and RMS error. The extent of cholinesterase inhibition was directly related to the magnitude of the HF HRV decrease, and was predicted by the weight-normalized PB dose. Cholinesterase inhibition was not related to the extent or severity of reported drug side effects.
CONCLUSIONS
PB does not appear to have detrimental physiological or performance consequences at the recommended 30-mg dose, or at twice that dose, when evaluated under non-stressful laboratory conditions.
Topics: Administration, Oral; Adolescent; Adult; Analysis of Variance; Cholinesterase Inhibitors; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Electroencephalography; Female; Heart Rate; Humans; Male; Pyridostigmine Bromide; Reaction Time; Task Performance and Analysis
PubMed: 12110996
DOI: 10.1007/s00213-002-1074-6 -
British Journal of Pharmacology Sep 1968
Topics: Cholinesterases; Electromyography; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Maternal-Fetal Exchange; Myasthenia Gravis; Neostigmine; Pregnancy; Pyridostigmine Bromide; Time Factors
PubMed: 5692081
DOI: No ID Found -
Nature Medicine Apr 1997
Topics: Animals; Blood-Brain Barrier; Brain; Humans; Hypertension; Mice; Neurons; Pyridostigmine Bromide; Stress, Physiological; Transcription, Genetic
PubMed: 9095157
DOI: 10.1038/nm0497-366a -
Neurology Jan 2017
Topics: Cholinesterase Inhibitors; Female; Humans; Myasthenia Gravis; Physicians; Pyridostigmine Bromide; Tracheostomy
PubMed: 28069973
DOI: 10.1212/WNL.0000000000003476 -
Anesthesiology Oct 1992
Review
Topics: Age Factors; Cholinesterase Inhibitors; Drug Interactions; Edrophonium; Humans; Neostigmine; Neuromuscular Blocking Agents; Pyridostigmine Bromide
PubMed: 1416176
DOI: 10.1097/00000542-199210000-00025 -
Biomedical Chromatography : BMC Mar 2024The present study focuses on the development of a simple, rapid, specific, and stability-indicating HPLC method for the simultaneous analysis of pyridostigmine bromide...
Stability indicating reversed-phase-high-performance liquid chromatography method development and validation for pyridostigmine bromide and sodium benzoate in oral solution.
The present study focuses on the development of a simple, rapid, specific, and stability-indicating HPLC method for the simultaneous analysis of pyridostigmine bromide (PGB) and sodium benzoate (SBN) in oral liquid dosage forms. Analytical techniques should enhance sensitivity and specificity for the estimation of pharmaceutical drug products. Stress studies were conducted under various International Conference on Harmonization (ICH) conditions for evaluation. The further optimized HPLC method was validated in accordance with the current ICH guidelines. Chromatographic separation was accomplished using a mobile phase consisting of a 950:50 v/v ratio of perchloric acid buffer and acetonitrile as mobile phase-A, and 100% acetonitrile as mobile phase-B. The flow rate is 1.0 mL/min, and the injection volume is 20 μL. Detection of components was carried out at 220 nm for PGB and 228 nm for SBN. The validated HPLC method demonstrated high specificity, with linearity ranging between 24 and 72 μg/mL for PGB and 5.2-15.6 μg/mL for SBN. The correlation coefficient for both drugs exceeded 0.999. The method demonstrated high accuracy, exceeding 97%. In stress studies, PGB was found to be sensitive to alkaline stress conditions. The results reveal the successful applicability of the current method for the estimation of PGB and SBN in its marketed formulation, which can be reasonably inferred to assess other formulation systems.
Topics: Sodium Benzoate; Chromatography, High Pressure Liquid; Pyridostigmine Bromide; Acetonitriles; Chromatography, Reverse-Phase; Drug Stability
PubMed: 38081595
DOI: 10.1002/bmc.5800 -
Practical Neurology Jun 2015Myasthenia gravis is an autoimmune disease of the neuromuscular junction for which many therapies were developed before the era of evidence based medicine. The basic... (Review)
Review
Myasthenia gravis is an autoimmune disease of the neuromuscular junction for which many therapies were developed before the era of evidence based medicine. The basic principles of treatment are well known, however, patients continue to receive suboptimal treatment as a result of which a myasthenia gravis guidelines group was established under the aegis of The Association of British Neurologists. These guidelines attempt to steer a path between evidence-based practice where available, and established best practice where evidence is unavailable. Where there is insufficient evidence or a choice of options, the guidelines invite the clinician to seek the opinion of a myasthenia expert. The guidelines support clinicians not just in using the right treatments in the right order, but in optimising the use of well-known therapeutic agents. Clinical practice can be audited against these guidelines.
Topics: Cholinesterase Inhibitors; Disease Management; Humans; Myasthenia Gravis; Neurology; Pyridostigmine Bromide; United Kingdom
PubMed: 25977271
DOI: 10.1136/practneurol-2015-001126