Background Prior studies have evaluated the use of various constituents of cannabis for their anti-seizure effects. Specifically, cannabidiol, a non-psychoactive component of cannabis, has been investigated for treatment-resistant epilepsy, but more information is needed particularly on its use in a pediatric population. Objective The objective of this study was to evaluate the pharmacokinetics and safety of a synthetic pharmaceutical-grade cannabidiol oral solution in pediatric patients with treatment-resistant epilepsy. Methods In this open-label study, pediatric patients (aged 1 to ≤ 17 years) with treatment-resistant epilepsy received cannabidiol oral solution administered as add-on to their current antiepileptic drug regimen. Patients received a single dose (5, 10, or 20 mg/kg) on day 1 and twice-daily dosing on days 4 through 10 (10-mg/kg [cohort 1], 20-mg/kg [cohort 2], or 40-mg/kg [cohort 3] total daily dose). Serial blood samples were collected on day 1 before dosing and up to 72 h post-dose, and on day 10 before dosing and up to 24 h post-dose. Blood samples to assess trough concentrations of cannabidiol were collected on day 6 (for patients aged 12 to ≤ 17 years), day 8 (for patients aged 2 to ≤ 17 years), and day 9 (for patients aged 6 to ≤ 17 years). Results Overall, 61 patients across three cohorts received one of three doses of cannabidiol oral solution (mean age, 7.6 years). The age composition was similar in the three cohorts. There was a trend for increased cannabidiol exposure with increased cannabidiol oral solution dosing, but overall exposure varied. Approximately 2–6 days of twice-daily dosing provided steady-state concentrations of cannabidiol. A bi-directional drug interaction occurred with cannabidiol and clobazam. Concomitant administration of clobazam with 40 mg/kg/day of cannabidiol oral solution resulted in a 2.5-fold increase in mean cannabidiol exposure. Mean plasma clobazam concentrations were 1.7- and 2.2-fold greater in patients receiving clobazam concomitantly with 40 mg/kg/day of cannabidiol oral solution compared with 10 mg/kg/day and 20 mg/kg/day. Mean plasma norclobazam values were 1.3- and 1.9-fold higher for patients taking clobazam plus 40 mg/kg/day of cannabidiol oral solution compared with the 10-mg/kg/day and 20-mg/kg/day groups. All doses were generally well tolerated, and common adverse events that occurred at > 10% were somnolence (21.3%), anemia (18.0%), and diarrhea (16.4%). Conclusions Inter-individual variability in systemic cannabidiol exposure after pediatric patient treatment with cannabidiol oral solution was observed but decreased with multiple doses. Short-term administration was generally safe and well tolerated. Trial Registration ClinicalTrials.gov (NCT02324673). Electronic supplementary material The online version of this article (10.1007/s40263-019-00624-4) contai...

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Comorbid hypertension was associated with increased risk of dementia, whereas antihypertensive medications, especially angiotensin-converting enzyme inhibitors and ARBs, were associated with reduced risk, even among patients without hypertension. Consequently, these agents may have potential therapeutic roles in delaying the onset of dementia in patients with diabetes.

These findings indicate that treatment with fentanyl sublingual spray results in effective relief of BTCP, with a rapid onset of action, and is well tolerated.

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BackgroundDronabinol, a pharmaceutical Δ-9-tetrahydrocannabinol, was originally developed as an oral capsule. This study evaluated the bioavailability of a new formulation, dronabinol oral solution, versus a dronabinol capsule formulation.MethodsIn an open-label, four-period, single-dose, crossover study, healthy volunteers were randomly assigned to one of two treatment sequences (T-R-T-R and R-T-R-T; T = dronabinol 4.25 mg oral solution and R = dronabinol 5 mg capsule) under fasted conditions, with a minimum 7-day washout period between doses. Analyses were performed on venous blood samples drawn 15 minutes to 48 hours postdose, and dronabinol concentrations were assayed by liquid chromatography–tandem mass spectrometry.ResultsFifty-one of 52 individuals had pharmacokinetic data for analysis. The 90% confidence interval of the geometric mean ratio (oral solution/capsule) for dronabinol was within the 80%–125% bioequivalence range for area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUC0–t) and AUC from time zero to infinity (AUC0–∞). Maximum plasma concentration was also bioequivalent for the two dronabinol formulations. Intraindividual variability in AUC0–∞ was >60% lower for dronabinol oral solution 4.25 mg versus dronabinol capsule 5 mg. Plasma dronabinol concentrations were detected within 15 minutes postdose in 100% of patients when receiving oral solution and in <25% of patients when receiving capsules.ConclusionSingle-dose dronabinol oral solution 4.25 mg was bioequivalent to dronabinol capsule 5 mg under fasted conditions. Dronabinol oral solution formulation may provide an easy-to-swallow administration option with lower intraindividual variability as well as more rapid absorption versus dronabinol capsules.

Several important factors were identified that are associated with increased dementia risk, and two factors were identified that are associated with reduced risk. It will be important to ascertain whether risk-factor modification reduces the HR for dementia in persons with diabetes, and to further examine effects of medication use for comorbid conditions.

The commercialization of systems for automated titration of insulin, referred to as artificial pancreas (AP) systems, for people with type 1 DM is close to becoming a reality due to the collaborative efforts of investigators in academia, funding agencies, and industry. The components of the AP system are subcutaneous insulin delivery pumps and continuous glucose sensors (CGM) and an algorithm. The AP system calculates the amount of insulin to be delivered at distinct time intervals using past and present CGM measurements and insulin delivery parameters. The AP systems should be designed to be safe and effective with consideration of the current devices' accuracy and reliability. Furthermore, the AP system should perform well despite relatively slow insulin action and the relatively fast effect of meal disturbances. The algorithm must account for device accuracy and reliability, the relatively slow pharmacodynamics of insulin, and the relatively fast effects of carbohydrate ingestion.Currently, there are numbers of publications from human trials demonstrating that AP systems can be deemed safe and effective for home use. The majority of the conducted AP trials were overnight studies, 1-7 with fewer full-day AP Background: Efficacy and safety of the Medtronic Hybrid Closed-Loop (HCL) system were tested in subjects with type 1 diabetes in a supervised outpatient setting.