Many of those who continued taking Palforzia as part of another trial were then shown to tolerate even higher doses, up to 2000 milligrams.
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The FDA said abusers of the drugs sometimes try to achieve "heroin-like highs" by taking massive doses, up to 300 milligrams at once.
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Products that contain 500 mg should follow the dosing regimen of adult doses up to 1,000 mg, not to exceed 4,000 mg in 24 hours.
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Vom Saal and his colleagues published a study in 2012 that found DEHP, a phthalate found in food packaging, had adverse reproductive effects in doses up to 20093,000 times lower than had been previously imagined.
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Single doses up to 500 times the recommended dose, as well as multiple doses up to 150 times the recommended dose for ten days, resulted in an increase of the mentioned side effects. Theses side effects were mild to moderate.
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LY-404,039 was the preferred drug candidate for further development due to its antipsychotic efficacy and lack of motor coordination effects at doses up to 30 mg/kg.
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Healthy adults taking regular doses up to 4,000mg a day show little evidence of toxicity. They are more likely to have abnormal liver function tests, but the importance of this is uncertain.
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In contrast, DMDA did not produce any hyperactivity in doses up to 100 μg.B. Costall, R. J. Naylor and R. M. Pinder (1976). "Characterisation of the mechanisms for hyperactivity induction from the nucleus accumbens by phenethylamine derivatives." Psychopharmacol.
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In preliminary human studies, oral intake of quercetin in doses up to one gram per day over three months did not cause adverse effects. The safety of using quercetin in dietary supplements during pregnancy and lactation has not been established.
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A meta-analysis concluded high-dosage (≥400 IU/d for at least 1 year) vitamin E was associated with an increase in all-cause mortality. A subsequent meta-analysis suggested no relationship with mortality at doses up to 5,500 IU/d, either positive or negative.
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Use of nifurtimox should be avoided in pregnant women due to limited use. There is limited data shown that nifurtimox doses up to 15 mg/kg daily can cause adverse effects in breastfed infants. Other authors do not consider breastfeeding a contraindication during nifurtimox use.
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A Phase I clinical trial of Senecavirus in adults with neuroendocrine tumors showed that senecavirus is apparently safe to administer at doses up to 1E11 vp/kg. It has potential antineoplastic activity.National Cancer Institute Definition of Seneca Valley virus-001. National Cancer Institute Retrieved on 2008-10-09.
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4-HO- MET produces psilocin-like distortion of color, sound, and form. Very little data exists about the pharmacological properties, metabolism, and toxicity of 4-HO-MET. There have been no reports of deaths from 4-HO-MET, even though people have reported taking doses up to 150 mg, more than an order of magnitude above the effective dose.
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The polymer-drug N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymer- doxorubicin (PK1; FCE28068) shows up to a 5 times reduction in anthracycline type toxicity compared to current treatments. Doses up to 1680 mg/m2 observed no cardiotoxicity. Antitumor behavior was observed at 80–320 mg/m2 of doxorubicin. Polymers are used for the delivery of drugs and proteins.
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Remogliflozin etabonate was shown to enhance urinary glucose excretion in rodents and humans. Early studies in diabetics improved plasma glucose levels. Remogliflozin etabonate has been studied at doses up to 1000 mg. A pair of 12-week phase 2b randomized clinical trials of diabetics published in 2015, found reductions in glycated hemoglobin and that it was generally well tolerated.
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The observed toxic dose in about 50% of these patients has been 0.3 g to 1.25 g of 12.5% amitraz formulations and 0.5 to 2 g of 20% formulations. The remaining patients took doses up to 10 g. Other frequently occurring symptoms after massive amitraz intoxication are CNS depression, respiratory depression, miosis, hypothermia, hyperglycemia, loss of consciousness, vomiting and bradycardia.
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SB-649868 is a dual orexin receptor antagonist in development by GlaxoSmithKline. The drug is currently in phase II development for insomnia. A phase I study evaluated doses up to 80 mg, resulting in significant improvement in sleep latency without adverse effects. In randomized, double- blind, placebo-controlled crossover trials, the 10 and 30 mg doses increased sleep time and reduced sleep latency.
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MDA Entry in PIHKAL At mild threshold dosages (around 10 mg) there are eyes-closed "dreams" with some body tingling, at higher doses (up to 140 mg) was reported to produce a pleasant, positive feeling. This compound is not anoretic at any dose. It lasts about 3 hours. Very little data exists about the pharmacological properties, metabolism, and toxicity of ALPHA.
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The exact mechanism of action of PRL-8-53 remains unknown. Doses up to 200 mg/kg are not observed to have stimulant properties, and a dosage of 20 mg/kg does not potentiate the effects of dextroamphetamine in rats. It displays possible cholinergic properties, and potentiates dopamine while partially inhibiting serotonin. PRL-8-53 reverses the catatonic and ptotic effects of reserpine.
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ICI-118,551 has been used in pre-clinical studies using murine models. When dissolved in saline, the compound crosses the blood–brain barrier. Common systemic doses used in rodent research are 0.5 or 1 mg/kg although efficacy has been demonstrated at doses as low as 0.0001 mg/kg in rhesus monkeys. Doses up to 20 mg/kg have been used without toxicity.
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By the late 1980s, two different compounds containing technetium-99m were introduced: teboroxime and sestamibi. The utilization of Tc-99m would allow higher doses (up to ) due to the shorter physical (6 hours) half life of Tc-99m. This would result in more decay, more scintillation and more information for the nuclear cameras to measure and turn into better pictures for the clinician to interpret.
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The Phase I study showed that doses up to 1000 mg of Abituzumab, cetuximab, and irinotecan were well tolerated. The results of Phase II showed that the primary endpoint of progression-free survival was not met, but overall survival improved in patients receiving Abituzumab compared to standard of care. The researchers postulate that this could be due to increased expression of αvβ6 integrin in tumors.
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The mode of action for ambazone has been studied extensively and has been shown to react via different methods. Ambazone shows low mutagenic activity and no cardiovascular, CNS, metabolic, or gastrointestinal side-effects with I.V. doses up to 10-5 mol/kg and oral doses up to 10-3 mol/kg. Ambazone can be administered via oral or I.V. administration, but the problem with oral administration is that one experimental study shows there is only a 35–50% absorption while another study shows 40% in the intestines; These results would tend to lead the reader to think that ambazone would not be the best choice for treatment, because with such a low absorbance, there is going to have to be a greater concentration ingested to gain a positive effect from the drug. The problem with a greater concentration is that ambazone has a half-life of 6–7 hours.
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They can eventually tolerate doses up to 35 times the LD50 without being intoxicated.de Araújo Pimenta L, de Almeida MES, Bretones ML et al. "Crotoxin promotes macrophage reprogramming towards an antiangiogenic phenotype", Scientific Reports, 9, 4281 (2019). doi:10.1038/s41598-019-40903-0. Preclinical studies on human patients also show that toxicity signs decreased or disappeared when the patients were exposed to crotoxin over longer periods of time.
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Hemilä H (2009) Vitamins and minerals. In:"Common cold" (Eccles R, Weber O, eds.) Birkhauser Verlag, pp. 275-307 Vitamin C does not decrease the frequency of colds in the general population, but it has halved the frequency of colds in people under heavy short-term physical stress. There is no effect of taking vitamin C in doses up to 8 grams per day after a cold has already begun.
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In a highly seasoned restaurant meal, intakes as high as 5000 mg or more may be possible (Yang et al. 1997). When very large doses of MSG (>5 g MSG in a bolus dose) are ingested, plasma glutamate concentration will significantly increase. However, the concentration typically returns to normal within two hours. In general, foods providing metabolizable carbohydrate significantly attenuate peak plasma glutamate levels at doses up to 150 mg/kg body weight.
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Similar to cisplatin and carboplatin, dicycloplatin also contains some side effects, which are nausea, vomiting, thrombocytopenia, neutropenia, anemia, fatigue, loss of appetite, liver enzyme elevation, and alopecia. However, with doses up to 350 mg/m(2), there is no significant toxicity; these effects are observed only at higher doses. Furthermore, the nephrotoxicity of dicycloplatin is reported to be less than that of cisplatin, and its myelosuppressive potency is similar to that of carboplatin.
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Zafirlukast is considered to be "pregnancy category B." This is due, in part, to the wide safety margin of zafirlukast in animal studies investigating teratogenicity. No teratogenicity has been observed in doses up to 2000 mg/kg/day in cynomolgus monkeys, representing an equivalent 20x exposure of the maximum recommended daily oral dose in human adults. However, spontaneous abortions occurred in cynomolgus monkeys at 2000 mg/kg/day, though the dose itself was maternally toxic.
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Generally speaking, it has been shown that chromium(III) picolinate is not toxic to humans. For most adults, it can be taken orally in doses up 1000 μg per day. This low toxicity has general been associated with low absorbance of Cr(III) in the body through the lungs, skin and gastrointestinal tract, coupled with high excretion. Normally, 99% of chromium(III) taken can be recovered in the feces of the user.
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No systemic side effects have been identified. The safety of taurolidine has also been confirmed in clinical studies with long-term intravenous administration of high doses (up to 20 grams daily). In the body, taurolidine is metabolized rapidly via the metabolites taurultam and methylol taurinamide, which also have a bactericidal action, to taurine, an endogenous aminosulphonic acid, carbon dioxide and water. Therefore, no toxic effects are known or expected in the event of accidental injection.
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The mechanism of action is through activation of the CB2 receptor leading to production of specialized proresolving eicosanoids such as lipoxin A4 and Prostaglandin J2. Studies in animals at doses up to 40 mg/kg show minimal psychoactivity of ajulemic acid, compared to that produced by tetrahydrocannabinol. A composition of ajulemic acid named Lenabasum (formerly Anabasum, Resunab) is being developed by Corbus Pharmaceuticals (formerly JB Therapeutics) for the treatment of orphan chronic life-threatening inflammatory diseases.
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Ten naval personnel were killed (8 officers and 2 enlisted men), probably by the explosion itself and not from radiation injuries. Radiation injuries were observed in 49 people, with 10 developing radiation sickness; the latter figure included mostly firefighters, some of whom sustained doses up to 220 rad (2.2 Gy) external and 400 rem (4 Sv) to the thyroid gland. Of the 2,000 involved in cleanup operations, 290 were exposed to high levels of radiation compared to normal standards.
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The drug is highly cardioselective at 5 mg. In addition, at doses above 10 mg, nebivolol loses its cardioselectivity and blocks both β1 and β2 receptors. (While the recommended starting dose of nebivolol is 5 mg, sufficient control of blood pressure may require doses up to 40 mg). Furthermore, nebivolol is also not cardioselective when taken by patients with a genetic makeup that makes them "poor metabolizers" of nebivolol (and other drugs) or with CYP2D6 inhibitors.
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Warfarin (brand name Coumadin) is a commonly prescribed blood thinner both in the inpatient and outpatient hospital settings. In pregnant women, warfarin is contraindicated and should be avoided as it crosses the placental barrier. Additionally, warfarin is listed as Pregnancy Category D, which means it has a risk of harming the fetus. However, it has been shown that daily warfarin doses up to 5 mg may be beneficial for pregnant women who are at higher risk of thromboembolism.
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The incorporation of Nva into peptides reflects the imperfect selectivity of the associated aminoacyl-tRNA synthetase. In Miller–Urey experiments probing prebiotic synthesis of amino acids, norvaline, but also norleucine, are produced. Norvaline is known to promote tissue regeneration and muscle growth, and to become a precursor in the penicillin biosynthetic pathway.reference.md Retrieved 4 September 2010 Norvaline has not been reported to be toxic at doses up to 5 grams a day, and it is commonly used by bodybuilders to increase muscle mass.
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Though its absolute bioavailability in humans is unknown, bicalutamide is known to be extensively and well-absorbed. Its absorption is not affected by food. The absorption of bicalutamide is linear at doses up to 150 mg/day and is saturable at doses above this, with no further increases in steady-state levels of bicalutamide occurring at doses above 300 mg/day. Whereas absorption of (R)-bicalutamide is slow, with levels peaking at 31 to 39 hours after a dose, (S)-bicalutamide is much more rapidly absorbed.
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The clinical cardiac safety of bilastine has been assessed in all of the clinical trials performed so far (more than 3,500 patients treated with bilastine) and in a phase I study (Thorough QT/QTc study) designed according to the ICH E14 guidance and the most demanding requirements from the Food and Drug Administration (FDA). When electrocardiograms (ECG) data from all of the phase I studies are analysed, no significant alteration is appreciated in any of the parameters after administering bilastine at single doses (up to 11 times the therapeutic dose), nor at multiple doses (up to 10 times the therapeutic dose). Phase II and III studies on AR and urticaria (including the open-label extension phase of 12 months) do not reveal alterations in the ECG, nor significant prolongations of the QTc interval after administration of bilastine 20 mg. The Thorough QT/QTc study was designed to assess the effect on the QT/QTc interval, both of the therapeutic dose (20 mg) and 100 mg of bilastine, but also the coadministration of the therapeutic dose with usual doses of ketoconazol (400 mg/day), a metabolism inhibitor and a P-gP dependent transport system.
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Valerylfentanyl is an opioid analgesic that is an analog of fentanyl and has been sold online as a designer drug. It has been seldom reported on illicit markets and there is little information about it, though it is believed to be less potent than butyrfentanyl but more potent than benzylfentanyl. In one study, it fully substituted for oxycodone and produced antinociception and oxycodone-like discriminative stimulus effects comparable in potency to morphine in mice, but failed to stimulate locomotor activity in mice at doses up to 100 mg/kg.
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The acutely toxic dose of aspirin is generally considered greater than 150 mg per kg of body mass. Moderate toxicity occurs at doses up to 300 mg/kg, severe toxicity occurs between 300 and 500 mg/kg, and a potentially lethal dose is greater than 500 mg/kg. Chronic toxicity may occur following doses of 100 mg/kg per day for two or more days. Monitoring of biochemical parameters such as electrolytes and solutes, liver and kidney function, urinalysis, and complete blood count is undertaken along with frequent checking of salicylate and blood sugar levels.
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A study was performed to assess the toxicity effects of doxorubicin-loaded polymeric nanoparticle systems. It was found that doses up to 400 mg/kg of PBCA nanoparticles alone did not cause any toxic effects on the organism. These low toxicity effects can most likely be attributed to the controlled release and modified biodistribution of the drug due to the traits of the nanoparticle delivery system. Toxicity is a highly important factor and limit of drug delivery studies, and a major area of interest in research on nanoparticle delivery to the brain.
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Acute and late CNS risks from space radiation are of concern for Exploration missions to the moon or Mars. Acute CNS risks include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks are possible neurological disorders such as Alzheimer's disease, dementia, or premature aging. The effect of the protracted exposure of the CNS to the low dose-rate (< 50 mGy h–1) of proton, HZE particles, and neutrons of the relevant energies for doses up to 2 Gy is of concern.
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The pharmacokinetics of besipirdine have been studied in conscious monkey. The calculated elimination half-life (t1/2) of besipirdine and P86-7480 after oral administration of 10, 20, and 40 mg/kg doses is 7.4 ± 2.1 hours. The t1/2 after intravenous administration of 10 mg/kg is 1.5 hours. Besipirdine is cleared through the kidneys at 0.13 ± 0.04 mL/min/kg; only 1% of the administered dose is excreted unused via the kidneys. In humans, using doses up to 30 mg, the t1/2 of besipirdine and P86-7480 were calculated as 3 hours, and 5.5–7 hours, respectively.
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The safety, tolerability, and pharmacokinetic profile of zaurategrast have been evaluated in 75 female and male healthy volunteers in three separate Phase 1 studies. Zaurategrast was well tolerated at oral doses up to 1000 mg given twice daily for 7 consecutive days with an adverse event profile comparable to that observed with placebo. There was no gender effect. The oral administration resulted in inhibition of VCAM-1 binding which could be maintained throughout a 12‑ or 24‑hour dose interval at well tolerated dosesBaker M, Shock A, Parton T et al. Pharmacokinetic and pharmacodynamic properties of the VLA-4 inhibitor CDP323.
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One effect of 5-HT2A receptor activation is a reduction in intraocular pressure, and so 5-HT2A agonists can be useful for the treatment of glaucoma. This has led to the development of compounds such as AL-34662 that are hoped to reduce pressure inside the eyes but without crossing the blood–brain barrier and producing hallucinogenic side effects. Animal studies with this compound showed it to be free of hallucinogenic effects at doses up to 30 mg/kg, although several of its more lipophilic analogues did produce the head-twitch response known to be characteristic of hallucinogenic effects in rodents.
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Research in animal models and clinical studies in alcoholic patients have found that tiapride has anxiolytic effects. Dopamine hyperactivity has been linked with alcohol withdrawal syndrome (AWS), suggesting that tiapride's antidopaminergic effects are the most likely mechanism for its clinical efficacy, although others believe some other mechanism might be involved. Alcoholic patients treated with tiapride at a dosage of 300 mg/day reported reduced psychological distress and improved abstinence from alcohol. In another study in which alcoholic patients were given titrated doses up to 800 mg/day, subjects showed significant improvements in ratings of withdrawal, craving, psychiatric symptoms and quality of life.
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A phase II clinical trial in the treatment of partial seizures demonstrated that the compound has efficacy in the treatment of partial seizures and a good safety profile. Since late 2006, the compound has been undergoing a large multicenter phase III clinical trial for the treatment of partial seizures. Its mechanism of action is unknown. A double-blind, placebo-controlled trial of carisbamate in 323 patients with migraine determined that carisbamate was well tolerated at doses up to 600 mg/day, but it failed to demonstrate that the drug was sufficiently more effective than placebo in migraine prophylaxis.
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Dehydronorketamine (DHNK), or 5,6-dehydronorketamine, is a minor metabolite of ketamine which is formed by dehydrogenation of its metabolite norketamine. Though originally considered to be inactive, DHNK has been found to act as a potent and selective negative allosteric modulator of the α7-nicotinic acetylcholine receptor (IC50 = 55 nM). For this reason, similarly to hydroxynorketamine (HNK), it has been hypothesized that DHNK may have the capacity to produce rapid antidepressant effects. However, unlike ketamine, norketamine, and HNK, DHNK has been found to be inactive in the forced swim test (FST) in mice at doses up to 50 mg/kg.
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In April 2009, Immutep announced its involvement in a Phase I study in pancreatic cancer conducted at Washington University School of Medicine in St. Louis, Missouri. This 18-patient study evaluated for safety the combination of efti with gemcitabine, a chemotherapy drug, at doses up to 2 mg. The combination was found to be safe, however no significant differences were observed when comparing pre- and post-treatment levels of monocytes, dendritic cells, and T cells, likely due to sub-optimal dosing. The results of the study were reported online in Investigational New Drugs in August 2012.
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The US military issued pyridostigmine bromide (PB) pills to protect against exposure to nerve gas agents such as sarin and soman. PB was used as a prophylactic against nerve agents; it is not a vaccine. Taken before exposure to nerve agents, PB was thought to increase the efficiency of nerve agent antidotes. PB had been used since 1955 for patients suffering from myasthenia gravis with doses up to 1,500 mg a day, far in excess of the 90 mg given to soldiers, and was considered safe by the FDA at either level for indefinite use and its use to pre-treat nerve agent exposure had recently been approved.
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The (R)-enantiomer of omeprazole is metabolized exclusively by the enzyme CYP2C19, which is expressed in very low amounts by 3% of the population. Treated with a normal dose of the enantiomeric mixture, these persons will experience blood levels five-times higher than those with normal CYP2C19 production. In contrast, esomeprazole is metabolized by both CYP2C19 and CYP3A4, providing less- variable drug exposure.Lemke TL, Williams DA, Roche VF, Zito SW. Foye's Principles of Medicinal Chemistry, 7th edition, Chapter 12 While omeprazole is approved only at doses of up to 20 mg for the treatment of gastroesophageal reflux, esomeprazole is approved for doses up to 40 mg.
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Around the world, codeine is, contingent on its concentration, a Schedule II and III drug under the Single Convention on Narcotic Drugs. In Australia, Canada, New Zealand, Sweden, the United Kingdom, the United States and many other countries, codeine is regulated under various narcotic control laws. In some countries it is available without a medical prescription in combination preparations from licensed pharmacists in doses up to 20 mg, or 30 mg when sold combined with 500 mg paracetamol. Of the European Union (EU) member states, 12 countries (Bulgaria, Cyprus, Denmark, Estonia, France, Ireland, Latvia, Lithuania, Malta, Poland, Romania, Slovenia) allow the sale of OTC codeine solid dosage forms.
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Their report concluded that Nomadic pastoralism through the adjacent areas would result in exposures of around 50µSV/a, however > Persons scavenging metals in the immediate vicinity of the E2 [test] tunnel > might receive doses up to 0.5mSv in 8 hours. Currently, external exposure > rates are less than one-tenth those existing in 1966. The study further found alpha particle emission from the solidified lava is roughly the same as the surrounding natural rock, which has some naturally occurring uranium. To date, some limited follow up by French personnel has taken place, but no long-term study of the native population, nor the aquifers in the area has been done.
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Some women regard spironolactone-induced breast enlargement as a positive effect. Spironolactone also commonly and dose-dependently produces gynecomastia (breast development) as a side effect in men. At low doses, the rate is only 5 to 10%, but at high doses, up to or exceeding 50% of men may develop gynecomastia. In the RALES, 9.1% of men taking 25 mg/day spironolactone developed gynecomastia, compared to 1.3% of controls. Conversely, in studies of healthy men given high-dose spironolactone, gynecomastia occurred in 3 of 10 (30%) at 100 mg/day, in 5 of 8 (62.5%) at 200 mg/day, and in 6 of 9 (66.7%) at 400 mg/day, relative to none of 12 controls.
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Arachidonic acid supplementation in daily doses of 1,000–1,500 mg for 50 days has been well tolerated during several clinical studies, with no significant side effects reported. All common markers of health, including kidney and liver function, serum lipids, immunity, and platelet aggregation appear to be unaffected with this level and duration of use. Furthermore, higher concentrations of ARA in muscle tissue may be correlated with improved insulin sensitivity. Arachidonic acid supplementation of the diets of healthy adults appears to offer no toxicity or significant safety risk. While studies looking at arachidonic acid supplementation in sedentary subjects have failed to find changes in resting inflammatory markers in doses up to 1,500 mg daily, strength-trained subjects may respond differently.
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The maximum recommended dose is 6 milliliters per day or 15 milliliters per week because of the risk of kidney problems, and it is not recommended to be used on consecutive days. Despite the potential for kidney problems when used at anesthetic doses, no significant adverse effects have been reported when it is used at the lower doses (up to 6 milliliters) used for pain relief. Due to the risk of kidney toxicity, methoxyflurane is contraindicated in people with pre- existing kidney disease or diabetes mellitus, and is not recommended to be administered in conjunction with tetracyclines or other potentially nephrotoxic or enzyme-inducing drugs. It is self-administered to children and adults using a hand-held inhaler device.
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The ANSM Committee found no evidence that the studies had been performed because the company had doubts as to the tolerance of the molecule. Notably absent from the protocol were calculations of receptor occupancy; predictions of in vivo ligand binding saturation levels; measures of target affinity or assessment of non-target binding interactions as suggested by the European guidance for Phase I studies (depending on whether BIA 10-2474 could be considered to require 'special consideration' as outlined in the guideline). On these issues, the French regulator's expert committee pointed out, based on the company's IC50 data, that complete FAAH inhibition should have been achieved with a dose of 1.25 mg in humans. In fact, the trial tested doses up to 80 times more (100 mg BIA 10-2474) than should have been required.
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The first clinical trial of GW280430A was conducted in a small cohort of healthy US volunteers (n=31) in December 1997 at the New York Presbyterian-Weill Cornell Medical Center, New York City. The study confirmed that, with propofol/fentanyl/N2O/O2 anesthesia, gantacurium (ED95 = 0.19 mg/kg) has a rapid onset of action (maximum neuromusuclar block ≤90 seconds at doses ranging from 2.5- to 3xED95) and an ultra-short duration of action (clinical duration of ≤10 minutes for doses up to 0.72 mg/kg). Additionally, the spontaneous recovery rate was rapid, predictable, and independent of dose administered (1- to 4xED95), indicating a lack of cumulative neuromuscular blocking effect: the 25–75% recovery index (indicating the rate of recovery) was 3 minutes, and complete recovery to TOF of 90% occurred ≤15 minutes (vs. ≤4 minutes after edrophonium administration).
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Gantacurium chloride is not associated with histamine release when administered as a rapid bolus (<5 seconds administration time) at doses up to and including 0.45 mg/kg (≤2.5xED95) according to one small study in healthy human volunteers. At 0.54 mg/kg (just under 3xED95 dose), one of four volunteers experienced histamine release with associated hypotension (30% maximum decrease in blood pressure and 13% maximum increase in heart rate) but no cutaneous flushing. At the highest administered dose of 0.72 mg/kg, three of four volunteers experienced histamine release with associated hypotension (17% to 34% maximum decrease in blood pressure and 16% to 25% increase in heart rate) and cutaneous flushing. These effects were transient and lasted no more than two minutes and did not require any adjunctive treatment to address the changes in blood pressure or heart rate.
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AB-001 (1-pentyl-3-(1-adamantoyl)indole) is a designer drug that was found as an ingredient in synthetic cannabis smoking blends in Ireland in 2010 and Hungary and Germany in 2011.Research on Head Shop drugs in Dublin: Part 2 It is unclear who AB-001 was originally developed by, but it is structurally related to compounds such as AM-1248 and its corresponding 1-(tetrahydropyran-4-ylmethyl) analogue, which are known to be potent cannabinoid agonists with moderate to high selectivity for CB2 over CB1. The first published synthesis and pharmacological evaluation of AB-001 revealed that it acts as a full agonist at CB1 (EC50 = 35 nM) and CB2 receptors (EC50 = 48 nM). However, AB-001 was found to possess only weak cannabimimetic effects in rats at doses up to 30 mg/kg, making it less potent than the carboxamide analogue APICA, which possesses potent cannabimimetic activity at doses of 3 mg/kg.
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AUC exhibits dose linearity for single doses up to 60 mg. Trospium chloride exhibits diurnal variability in exposure with a decrease in Cmax and AUC of up to 59% and 33%, respectively, for evening relative to morning doses. Administration with a high fat meal resulted in reduced absorption, with AUC and Cmax values 70 to 80% lower than those obtained when trospium chloride was administered while fasting. Therefore, it is recommended that trospium chloride should be taken at least one hour prior to meals or on an empty stomach. Protein binding ranged from 50 to 85% when concentration levels of trospium chloride (0.5 to 50 ng/mL) were incubated with human serum in vitro. The 3H-trospium chloride ratio of plasma to whole blood was 1.6:1. This ratio indicates that the majority of 3H-trospium chloride is distributed in plasma. The apparent volume of distribution for a 20 mg oral dose is 395 (± 140) liters.
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Ocfentanil (INN; also called A-3217) is a potent synthetic opioid structurally related to fentanyl that was developed in the early 1990s as one of a series of potent naloxone-reversible opioids in an attempt to obtain an opioid that had better therapeutic indices in terms of cardiovascular effects and respiratory depression as compared to fentanyl. Ocfentanil was never developed for medical use despite reasonable results in human clinical trials, but subsequently started to be sold as a designer drug starting in around 2013. Study of the analgesic activity of ocfentanil using the mouse hot plate test (55 °C) gave an ED50 of 0.007 mg/kg compared to 0.018 mg/kg for fentanyl; ocfentanil being approximately 2.5 times as potent as fentanyl in this test. In human volunteers ocfentanil induces effective analgesia at 1 μg/kg, while in doses up to 3 μg/kg, analgesia and respiratory depression occurred in a dose-dependent manner.
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