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Purpose

Morphine ARER is a novel oral, abuse-deterrent, extended-release (ER) formulation of morphine sulfate with physical and chemical properties that deter misuse and abuse by nonoral routes of administration. Here we evaluate the relative bioavailability of morphine ARER and extended-release morphine.

Methods

This single-dose, 2-treatment, 2-period, 2-sequence, randomized crossover study in healthy adult subjects compared the relative bioavailability of morphine ARER 100 mg to that of ER morphine 100 mg in the fasted condition. At 12 and 1.5 hours before dosing and 12 hours after dosing, all subjects received a 50-mg oral naltrexone tablet to minimize opioid-related side effects. Pharmacokinetic parameters including the AUC0–t, AUC0–∞, and Cmax of morphine and its metabolite morphine-6-glucuronide (M6G) were determined at various times up to 48 hours postdose. The bioequivalence of morphine ARER and ER morphine was determined using an ANOVA of the least-squares mean values of morphine and M6G bioavailability.

Findings

Forty-nine subjects completed the study. Both morphine ARER and ER morphine exhibited peak plasma morphine and M6G concentrations of ~30 ng/mL and ~200 ng/mL, respectively, at 3 hours postdose. The 90% CIs of the ln-transformed values of morphine AUC0–t, AUC0–∞, and Cmax were within the 80% to 125% range for bioequivalence. M6G values also indicated bioequivalence of morphine ARER and ER morphine. The most common adverse events were nausea and somnolence.

Implications

These data show that, in these subjects, morphine ARER was bioequivalent to ER morphine, a treatment for pain with well-established efficacy and safety profiles.  相似文献   
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Clinical Rheumatology - The aim of this study is to evaluate a possible negative action of lockdown, during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, in the...  相似文献   
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Our aim was to evaluate incidence and riskfactors of liver involvement in obese Italian childrenas assessed by both ultrasonographic and biochemicalparameters. In seventy-five consecutive obese children (age 9.5 ± 2.9 years, males/females41/34), serum levels of enzymes and ultrasonography ofthe liver were evaluated. Tests were repeated one,three, and six months after starting a moderatehypocaloric diet and an exercise program. Three obese childrenwho were found to have chronic viral hepatitis wereexcluded from the study. Thirty-eight of 72 (53%) obesechildren had an ultrasonographic image of bright liver consistent with liver steatosis. Thelatter was severe in nine children, moderate in 16, andmild in 13. Eighteen obese children (25%) had elevatedtransaminase levels. Bright liver andhypertransaminasemia were not due to any of the most common causesof liver disease. Both were rapidly responsive to lossof weight, confirming that liver involvement wassecondary to obesity and that steatosis orsteatohepatitis rather than fibrosis were involved. Obesityduration not more than three years (odds ratio = 4.77),a higher degree of obesity (odds ratio = 2.09), andhypertransaminasemia (odds ratio = 2.15) appeared asimportant predictive factors of liver involvement atultrasonography. Incidence of liver involvement assessedby means of ultrasonography is significantly higher thanthat revealed by measurement of serum liver enzymes. A short duration of obesity emerged as apotentially new risk factor of liver involvement in thepediatric obese population and needs to be confirmed infuture studies.  相似文献   
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