1.Pharmacokinetics and Safety of Migalastat HCl and Effects on Agalsidase Activity in Healthy Volunteers.
Johnson FK1, Mudd PN Jr2, Bragat A3, Adera M3, Boudes P3. Clin Pharmacol Drug Dev. 2013 Apr;2(2):120-32. doi: 10.1002/cpdd.1. Epub 2013 Feb 21.
Migalastat HCl is an investigational, oral treatment for Fabry disease, an X-linked lysosomal storage disorder. Four Phase 1 studies were conducted to determine the pharmacokinetics, pharmacodynamics, safety, and tolerability of migalastat. Healthy volunteers (N = 124), 18-55 years old, received migalastat HCl single (25 mg-2000 mg) or twice-daily doses (50 mg, 150 mg) for 7 days in a double-blind, placebo-controlled fashion. Migalastat pharmacokinetics were dose-proportional (AUC∞ range: 1129-72 838 ng h/mL, Cmax range: 200.5-13 844 ng/mL, t1/2 3-4 hours). Steady state was achieved by Day 7. Up to 67% of the dose was excreted as unchanged drug in urine. Increased α-Gal A activity was dose related. No abnormal cardiac effects, including prolonged QTc intervals, were observed. The pharmacokinetics of migalastat were well characterized in these Phase 1 studies conducted healthy volunteers. The 150 mg dose of migalastat HCl administered BID for 7 days was generally safe and well tolerated.
2.Methylphenidate HCL for the Treatment of ADHD in Children and Adolescents.
Childress AC1. Expert Opin Pharmacother. 2016 Apr 26. [Epub ahead of print]
INTRODUCTION: Since Ritalin (methylphenidate immediate-release or MPH IR) was first marketed in 1955, it has been a mainstay of treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). Areas covered: The postulated mechanism of action, adverse events and efficacy of MPH are examined. MPH formulations that are currently on the market in the United States and those that will soon be available are considered. Various products are examined by comparing onset of effect and duration of action. Expert opinion: MPH has a well-known efficacy and safety profile. The development of extended-release (MPH-ER) was a significant advance in ADHD treatment. Recent products offer convenience in terms of dosing and timing of drug administration to improve symptom control, but efficacy is similar among all MPH-ER products. One formulation may be more appropriate for an individual patient, but no product offers significant advantages over all others. Since MPH is only effective in about 80% of patients, identifying factors that predict drug response is an active area of research.
3.Enantioselective Oxetane Ring Opening with Chloride: Unusual Use of Wet Molecular Sieves for the Controlled Release of HCl.
Yang W1, Wang Z1, Sun J2. Angew Chem Int Ed Engl. 2016 Apr 28. doi: 10.1002/anie.201601844. [Epub ahead of print]
An unprecedented enantioselective oxetane opening with chloride provides access to a range of highly functionalized three-carbon building blocks. The excellent enantiocontrol is enabled by not only a new catalyst, but also by the unusual use of wet molecular sieves for the controlled release of HCl.