Pyridostigmine to Reduce the duration of postoperative Ileus after Colorectal surgery (PyRICo-RCT): randomized clinical 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).

Coincidental Onset of Ocular Myasthenia Gravis Following ChAdOx1 n-CoV-19 Vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

BACKGROUND: The Oxford-AstraZeneca vaccine ChAdOx1 (AZD1222, Vaxzevria) is playing a crucial role in counteracting the coronavirus disease-2019 (COVID-19) pandemic [1]. Since March 2021, reports of unexpected thrombotic events associated with thrombocytopenia and vaccination have been published [2]. To the best of our knowledge there is only one report about vaccination-associated myasthenia gravis (MG) occurring after a second dose of BNT162b2 (Pfizer-BioNTech).

Overactive bladder in patients with myasthenia gravis-A cross-sectional population-based study.

BACKGROUND: In myasthenia gravis (MG), first-line treatment for MG is acetylcholinesterase inhibitors which alleviates symptoms, but concomitantly may cause autonomic adverse effects. AIMS OF THE STUDY: In this study, we evaluated if symptoms of overactive bladder (OAB) are more frequent among MG patients than healthy controls. METHODS: Eighty-three MG patients and 50 healthy sex- and age-matched controls were included and answered the questionnaire "International Consultation on Incontinence Questionnaire Overactive Bladder Module" (ICIQ-OAB), including questions about polyuria, nocturia, urgency, and stress incontinence. Clinical severity of MG was determined based on three standardized clinical evaluations. RESULTS: Compared to control subjects, MG patients had a higher total OAB score (median 5 [range 0-12] versus 3 [0; 7]) (p < 0.005) with higher scores concerning all four items. Also, MG patients had a higher bother score (10 [0-40] versus 5 [0-40]) (p < 0.05). Patients receiving a daily dose of pyridostigmine of more than 300 mg had a higher OAB score than other patients. CONCLUSIONS: Myasthenia gravis patients have more bothering symptoms of OAB than healthy controls, related to the daily dose of pyridostigmine. To minimize adverse effects in patients with symptoms of OAB, the pyridostigmine dose should be as low as possible.

Coagulation Effect of Sugammadex as Determined by Thromboelastography in a Randomized Controlled Study of Surgical Patients.

Introduction: Sugammadex has been shown to be associated with prolongation of prothrombin time and activated partial thromboplastin time. However, it is not known whether it could be associated with enhancing postoperative hypocoagulation. The objective of this study was to analyze the effect of 4 mg/kg of sugammadex on thromboelastography (TEG) parameters in surgical patients. Methods: After Institutional Review Board approval, a prospective double-blinded randomized controlled study was conducted between September 2016 and April 2017. Sixty adult patients scheduled for laparoscopic abdominal surgery were randomly allocated to receive either sugammadex 4 mg/kg (sugammadex group) or pyridostigmine 0.15 mg/kg in combination with glycopyrrolate 0.4 mg (control group) to reverse rocuronium-induced neuromuscular blockade at the completion of surgery. Blood samples were collected three time points; After the final suture of surgery (baseline) (T1), and at 10 min (T2) and 1 h (T3) after administration of the study drug. Whole blood was analyzed by TEG using TEG 5000 (Hemonetics Corp, Braintree, MA, USA). The primary endpoints were comparison of coagulation time (K, time to 20 mm clot amplitude), R (reaction time), alpha angle, and maximal amplitude (MA) between two groups. Results: Coagulation time was significantly prolonged in sugammadex group after 10 min of the study drug administration compared to control group (mean value 1.3 ± 0.4 vs. 1.5 ± 0.4, P = 0.03). However, R, alpha angle and MA value were not different between two groups. Conclusions: Sugammadex 4 mg/kg showed an increase in coagulation time in surgical patients. Physician should aware the potential enhancement of hypocoagulation by sugammadex in the setting of high risk of postoperative bleeding.

Coronary spastic angina after the administration of intravenous immunoglobulin in myasthenia gravis: a case report.

BACKGROUND: Myasthenia gravis (MG) is an autoimmune disease caused by antibodies that block or destroy nicotinic acetylcholine receptors at the neuromuscular junction. Most of MG patients need immunosuppression agents in addition to treatments that alleviate the symptoms. Intravenous immunoglobulin (IVIg) and plasma exchange are specific treatments given to patients with severe MG and myasthenia gravis crisis. IVIg therapy can cause an increase in serum viscosity; therefore, the risk for thromboembolic events, such as stroke, myocardial infarction, and pulmonary embolism, are reported after IVIg therapy. CASE PRESENTATION: An MG patient was treated with pyridostigmine bromide and prednisolone. The patient's symptoms worsened 26 days after the commencement of treatment and was presented with head drop and dyspnea. The patient was diagnosed with MG crisis and IVIg was initiated. However, the patient reported chest pain and dyspnea 3 days after IVIg had started. An electrocardiogram (ECG) revealed ST elevations in leads II, III, and aVF. A cardiac catheterization was performed and stenosis, obstruction, and sclerosis were ruled out. Glyceryl trinitrate relieved the patient's symptoms, suggesting coronary spastic angina (CSA). CONCLUSIONS: We report the first case of CSA after IVIg. Practitioners should be aware of the potential risks of CSA when administering IVIg for MG patients, in particular in old patients with vascular risk factors.

Combined Pre- and Posttreatment of Paraoxon Exposure.

AIMS: Organophosphates (OPCs), useful agents as pesticides, also represent a serious health hazard. Standard therapy with atropine and established oxime-type enzyme reactivators is unsatisfactory. Experimental data indicate that superior therapeutic results can be obtained when reversible cholinesterase inhibitors are administered before OPC exposure. Comparing the protective efficacy of five such cholinesterase inhibitors (physostigmine, pyridostigmine, ranitidine, tacrine, or K-27), we observed best protection for the experimental oxime K-27. The present study was undertaken in order to determine if additional administration of K-27 immediately after OPC (paraoxon) exposure can improve the outcome. METHODS: Therapeutic efficacy was assessed in rats by determining the relative risk of death (RR) by Cox survival analysis over a period of 48 h. Animals that received only pretreatment and paraoxon were compared with those that had received pretreatment and paraoxon followed by K-27 immediately after paraoxon exposure. RESULTS: Best protection from paraoxon-induced mortality was observed after pretreatment with physostigmine (RR = 0.30) and K-27 (RR = 0.34). Both substances were significantly more efficacious than tacrine (RR = 0.67), ranitidine (RR = 0.72), and pyridostigmine (RR = 0.76), which were less efficacious but still significantly reduced the RR compared to the no-treatment group (paraoxon only). Additional administration of K-27 immediately after paraoxon exposure (posttreatment) did not further reduce mortality. Statistical analysis between pretreatment before paraoxon exposure alone and pretreatment plus K-27 posttreatment did not show any significant difference for any of the pretreatment regimens. CONCLUSIONS: Best outcome is achieved if physostigmine or K-27 are administered prophylactically before exposure to sublethal paraoxon dosages. Therapeutic outcome is not further improved by additional oxime therapy immediately thereafter.

Pyridostigmine bromide and stress interact to impact immune function, cholinergic neurochemistry and behavior in a rat model of Gulf War Illness.

Gulf War Illness (GWI) is characterized by a constellation of symptoms that includes cognitive dysfunction. While the causes for GWI remain unknown, prophylactic use of the acetylcholinesterase inhibitor pyridostigmine bromide (PB) in combination with the stress of deployment has been proposed to be among the causes of the cognitive dysfunction in GWI. Mechanistically, clinical studies suggest that altered immune function may be an underlying factor in the neurochemical and neurobehavioral complications of GWI. Accordingly, the goal of this study was to determine how responses to an immune challenge (lipopolysaccharide; LPS) or stress impacts inflammation, acetylcholine (ACh) neurochemistry and behavior in an experimental model of GWI. Rats with a history of PB treatment exhibited potentiated increases in C-reactive protein levels in response to a submaximal LPS challenge compared to control rats, indicating that prior treatment with this cholinesterase inhibitor leads to exacerbated inflammatory responses to a subsequent immune challenge. ACh responses to LPS administration were decreased in the hippocampus, but not prefrontal cortex (PFC), in rats with a prior history of PB treatment or stress exposure. Additionally, ACh release in response to acute immobilization stress was attenuated in the PFC and hippocampus in these groups. These attenuated cholinergic responses were accompanied by impairments in contextual and cue-based fear learning. The results of this study suggest that stress and LPS challenges adversely affect central ACh neurochemistry in a rodent model of GWI and support the hypothesis that dysregulated immune responses are mechanistically linked to the neurological complications of GWI.

Ocular Myasthenia Induced by Rivaroxaban in Patient with Deep Vein Thrombosis.

The non-vitamin K antagonist oral anticoagulant rivaroxaban is indicated in prevention and treatment of venous thromboembolism (VTE). A 60-year-old male patient complained of bilateral ptosis after administration of rivaroxaban for deep vein thrombosis (DVT). Myasthenia gravis (MG) was confirmed by positive serum antiacetylcholine receptor antibody test. No mediastinal thymoma was found. The ocular myasthenia reversed after discontinuing rivaroxaban treatment. Nevertheless, ptosis recurred and chronic oral pyridostigmine bromide treatment was necessary. The mechanism of MG development by rivaroxaban therapy is not completely understood. The development of rivaroxaban-induced autoimmune disease could be based on cross-reactivity between antibodies against rivaroxaban-derived antigens or by T-cell activation. To our knowledge, this report of ocular myasthenia by rivaroxaban administration is the first in the literature. Despite the benefits of rivaroxaban, it is important to recognize unexpected immune-related adverse events.

Long-term administration of pyridostigmine attenuates pressure overload-induced cardiac hypertrophy by inhibiting calcineurin signalling.

Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload-induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and ß-myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN/NFAT3/GATA4 pathway and suppressed Orai1/STIM1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN/NFAT3/GATA4 pathway and suppression of the interaction of Orai1/STIM1.

Prescription profile of pyridostigmine use in a population of patients with myasthenia gravis.

We determined the pyridostigmine prescription pattern in a population of patients with myasthenia gravis (MG). A descriptive cross-sectional study was conducted by using a prescription database of 3.5 million individuals from which patients who had been diagnosed with MG and for whom pyridostigmine had been prescribed were selected. A total of 306 outpatients with MG were found, and 258 were receiving pyridostigmine (mean age 53.0 ± 18.0 years). The calculated prevalence of MG was 86.7 cases per million persons. Monotherapy was used by 53.1% of the patients, prednisolone was used by 21.7%, and 30.2% used other immunomodulators. Medications for other comorbidities were taken by 74.8% of the patients, and 43.4% had prescriptions that could potentially trigger worsening symptoms. Pyridostigmine is being prescribed at doses close to the defined daily doses predominantly as monotherapy. A high proportion of patients were also prescribed a medication that could aggravate their condition, including some that can trigger a myasthenic crisis. Muscle Nerve 56: 1041-1046, 2017.

Persistent modification of Nav1.9 following chronic exposure to insecticides and pyridostigmine bromide.

Many veterans of the 1991 Gulf War (GW) returned from that conflict with a widespread chronic pain affecting deep tissues. Recently, we have shown that a 60day exposure to the insecticides permethrin, chlorpyrifos, and pyridostigmine bromide (NTPB) had little influence on nociceptor action potential forming Nav1.8, but increased Kv7 mediated inhibitory currents 8weeks after treatment. Using the same exposure regimen, we used whole cell patch methods to examine whether the influences of NTPB could be observed on Nav1.9 expressed in muscle and vascular nociceptors. During a 60day exposure to NTPB, rats exhibited lowered muscle pain thresholds and increased rest periods, but these measures subsequently returned to normal levels. Eight and 12weeks after treatments ceased, DRG neurons were excised from the sensory ganglia. Whole cell patch studies revealed little change in voltage dependent activation and deactivation of Nav1.9, but significant increases in the amplitude of Nav1.9 were observed 8weeks after exposure. Cellular studies, at the 8week delay, revealed that NTPB also significantly prolonged action potential duration and afterhyperpolarization (22°C). Acute application of permethrin (10µM) also increased the amplitude of Nav1.9 in skin, muscle and vascular nociceptors. In conclusion, chronic exposure to Gulf War agents produced long term changes in the amplitude of Nav1.9 expressed in muscle and vascular nociceptors. The reported increases in Kv7 amplitude may have been an adaptive response to increased Nav1.9, and effectively suppressed behavioral pain measures in the post treatment period. Factors that alter the balance between Nav1.9 and Kv7 could release spontaneous discharge and produce chronic deep tissue pain.

[Pyridostigmine in the treatment of postural orthostatic tachycardia syndrome]. / Postüral ortostatik tasikardi sendromunda piridostigmin tedavisi.

A 34-year-old female patient was admitted with the complaints of inability to stand upright, palpitations, dizziness, and fatigue in the upright posture for the last one year. She was found to stand upright for less than one minute without symptoms. Tilt table testing showed that, compared to baseline her heart rate increased 55 beats/min in the fifth minute of the test with the symptoms of palpitations, fatigue and sweating without any significant change in her blood pressure. Postural orthostatic tachycardia syndrome was diagnosed, and pyridostigmine treatment was started. Four months after treatment her symptoms were relieved so that she was able to function as a nurse.

A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation.

OBJECTIVES: Chronic constipation in diabetes mellitus is associated with colonic motor dysfunction and is managed with laxatives. Cholinesterase inhibitors increase colonic motility. This study evaluated the effects of a cholinesterase inhibitor on gastrointestinal and colonic transit and bowel function in diabetic patients with constipation. DESIGN: After a 9-day baseline period, 30 patients (mean ± SEM age 50 ± 2 years) with diabetes mellitus (18 type 1, 12 type 2) and chronic constipation without defaecatory disorder were randomised to oral placebo or pyridostigmine, starting with 60 mg three times a day, increasing by 60 mg every third day up to the maximum tolerated dose or 120 mg three times a day; this dose was maintained for 7 days. Gastrointestinal and colonic transit (assessed by scintigraphy) and bowel function were evaluated at baseline and the final 3 and 7 days of treatment, respectively. Treatment effects were compared using analysis of covariance, with gender, body mass index and baseline colonic transit as covariates. RESULTS: 19 patients (63%) had moderate or severe autonomic dysfunction; 16 (53%) had diabetic retinopathy. 14 of 16 patients randomised to pyridostigmine tolerated 360 mg daily; two patients took 180 mg daily. Compared with placebo (mean ± SEM 1.98 ± 0.17 (baseline), 1.84 ± 0.16 (treatment)), pyridostigmine accelerated (1.96 ± 0.18 (baseline), 2.45 ± 0.2 units (treatment), p<0.01) overall colonic transit at 24 h, but not gastric emptying or small-intestinal transit. Treatment effects on stool frequency, consistency and ease of passage were significant (p ≤ 0.04). Cholinergic side effects were somewhat more common with pyridostigmine (p=0.14) than with placebo. CONCLUSIONS: Cholinesterase inhibition with oral pyridostigmine accelerates colonic transit and improves bowel function in diabetic patients with chronic constipation.

Prolonged administration of pyridostigmine impairs neuromuscular function with and without down-regulation of acetylcholine receptors.

BACKGROUND: The acetylcholinesterase inhibitor, pyridostigmine, is prophylactically administered to mitigate the toxic effects of nerve gas poisoning. The authors tested the hypothesis that prolonged pyridostigmine administration can lead to neuromuscular dysfunction and even down-regulation of acetylcholine receptors. METHODS: Pyridostigmine (5 or 25 mg·kg·day) or saline was continuously administered via osmotic pumps to rats, and infused for either 14 or 28 days until the day of neuromuscular assessment (at day 14 or 28), or discontinued 24 h before neuromuscular assessment. Neurotransmission and muscle function were examined by single-twitch, train-of-four stimulation and 100-Hz tetanic stimulation. Sensitivity to atracurium and acetylcholine receptor number (quantitated by I-α-bungarotoxin) provided additional measures of neuromuscular integrity. RESULTS: Specific tetanic tensions (Newton [N]/muscle weight [g]) were significantly (P < 0.05) decreased at 14 (10.3 N/g) and 28 (11.1 N/g) days of 25 mg·kg·day pyridostigmine compared with controls (13.1-13.6 N/g). Decreased effective dose (0.81-1.05 vs. 0.16-0.45 mg/kg; P < 0.05) and decreased plasma concentration (3.02-3.27 vs. 0.45-1.37 µg/ml; P < 0.05) of atracurium for 50% paralysis (controls vs. 25 mg·kg·day pyridostigmine, respectively), irrespective of discontinuation of pyridostigmine, confirmed the pyridostigmine-induced altered neurotransmission. Pyridostigmine (25 mg·kg·day) down-regulated acetylcholine receptors at 28 days. CONCLUSIONS: Prolonged administration of pyridostigmine (25 mg·kg·day) leads to neuromuscular impairment, which can persist even when pyridostigmine is discontinued 24 h before assessment of neuromuscular function. Pyridostigmine has the potential to down-regulate acetylcholine receptors, but induces neuromuscular dysfunction even in the absence of receptor changes.

Usefulness of administration of non-organophosphate cholinesterase inhibitors before acute exposure to organophosphates: assessment using paraoxon.

Reversible acetylcholinesterase (AChE) inhibitors can protect against the lethal effects of irreversible organophosphorus AChE inhibitors (OPCs), when administered before OPC exposure. We have assessed in vivo the mortality-reducing efficacy of a group of known AChE inhibitors, when given in equitoxic dosage before exposure to the OPC paraoxon. Protection was quantified in rats by determining the relative risk (RR) of death. Best in vivo protection from paraoxon-induced mortality was observed after prophylactic administration of physostigmine (RR = 0.30) or the oxime K-27 (RR = 0.34); both treatments were significantly superior to the pre-treatment with all other tested compounds, including the established substance pyridostigmine. Tacrine (RR = 0.67), ranitidine (RR = 0.72), pyridostigmine (RR = 0.76), tiapride (RR = 0.80) and 7-MEOTA (RR = 0.86) also significantly reduced the relative risk of paraoxon-induced death, but to a lesser degree. Methylene blue, amiloride and metoclopramide had an unfavorable effect (RR ≥ 1), significantly increasing mortality. When CNS penetration by prophylactic is undesirable K-27 is a promising alternative to pyridostigmine.

Design and evaluation of an economic taste-masked dispersible tablet of pyridostigmine bromide, a highly soluble drug with an extremely bitter taste.

Pyridostigmine bromide (PTB) is a highly soluble and extremely bitter drug. Here, an economic complexation technology combined with direct tablet compression method has been developed to meet the requirements of a patient friendly dosage known as taste-masked dispersible tablets loaded PTB (TPDPTs): (1) TPDPTs should have optimal disintegration and good physical resistance (hardness); (2) a low-cost, simple but practical preparation method suitable for industrial production is preferred from a cost perspective. Physicochemical properties of the inclusion complex of PTB with beta-cyclodextrin were investigated by Fourier transformed infrared spectroscopy, differential scanning calorimetry and UV spectroscopy. An orthogonal design was chosen to properly formulate TPDPTs. All volunteers regarded acceptable bitterness of TPDPTs. The properties including disintegration time, weight variation, friability, hardness, dispersible uniformity and drug content of TPDPTs were evaluated. The dissolution profile of TPDPTs in distilled water exhibited a fast rate. Pharmacokinetic results demonstrated that TPDPTs and the commercial tablets were bioequivalent.

Preparation and characterization of poly(lactic acid) nanoparticles for sustained release of pyridostigmine bromide.

A novel pyridostigmine bromide poly (lactic acid) nanoparticles (PBPNPs) was prepared to obtain sustained release characteristics of PB. A central composite design approach was employed for process optimization. The in vitro release studies were carried out by dialysis method and conducted using four different dissolution media. Similar factor method was investigated for dissolution profile comparison. Multiple linear regression analysis for process optimization revealed that the optimal PBPNPs were obtained where the values of the amount of PB (X1, mg), PLA concentration (X2, % w:v), and PVA concentration (X3, % w:v) were 49.20 mg, 3.31% and 3.41%, respectively. The average particle size and zeta potential of PBPNPs with the optimized formulation were 722.9 +/- 4.3 nm, and -25.12 +/- 1.2 mV, respectively. PBPNPs provided an initial burst of drug release followed by a very slow release over an extended period of time (72 h). Compared with free PB, PBPNPs had a significantly lower release rate of PB in vitro. The in vitro release profile of the PBPNPs could be described by Weibull models, regardless of type of dissolution medium. Statistical significance of similarity between every two dissolution profiles of PBPNPs in different dissolution media was found, and the difference between the curves of PBPNPs and pure PB was statistically significant.

[Preparation and quality control of pyridostigmine bromide orally disintegrating tablet].

OBJECTIVE: To prepare orally disintegrating tablets containing pyridostigmine bromide and optimize formulations. METHODS: Solid dispersion was prepared using solvent evaporation-deposition method. The formulation was optimized by central composite design-response surface methodology (RSM plus CCD) with disintegration time as a reference parameter. RESULTS: The orally disintegrating tablets showed integrity and were smooth with desirable taste and feel in mouth. The disintegration time was less than 30 s. The cumulative drug dissolution was around 8.5% (around 2.5 mg which was less than bitterness threshold of pyridostigmine bromide of 3 mg) within 5 min in water while the cumulative drug dissolution was higher than 95% within 2 min in 0.1 N HCl. CONCLUSION: The orally disintegrating tablets are reasonable in formulation, feasible in technology and patient-friendly.