Background/Purpose
Ethanol co-administered with immediate-release dl-methylphenidate (dl-MPH) or dexmethylphenidate (d-MPH) significantly increases the geomean maximum plasma concentration (Cmax) of d-MPH 22% and 15%, respectively, and elevates overall drug exposure and psychostimulant effects. We asked the question: Are these ethanol-MPH interactions based more fundamentally on: (1) inhibition of post-absorption d-MPH metabolism or (2) acceleration of MPH formulation gastric dissolution by ethanol in the stomach? This was investigated using the pulsatile, distinctly biphasic, Spheroidal Oral Drug Absorption Systems of dl-MPH and d-MPH.
Methods/Procedures
In a randomized, 4-way crossover study, fourteen healthy subjects received pulsatile dl-MPH (40 mg) or d-MPH (20 mg), with or without ethanol (0.6 g/kg), dosed 4 hours later. These 4 hours allowed the delayed-release second MPH pulse to reach a more distal region of the gut to preclude gastric biopharmaceutical influences. Plasma was analyzed using a highly sensitive chiral method. Subjective/physiological effects were recorded.
Findings/Results
Ethanol increased the second pulse of d-MPH Cmax for dl-MPH by 35% (P < 0.01), and the partial area under the curve (pAUC4–8h) by 25% (P < 0.05). The respective values for enantiopure d-MPH were 27% (P = 0.001) and 20% (P < 0.01). The carboxylesterase 1-mediated transesterification metabolite ethylphenidate served as a biomarker for co-exposure. Ethanol significantly potentiated stimulant responses to either formulation.
Implications/Conclusions
These findings support drug dispositional interactions between ethanol and MPH as dominant over potential biopharmaceutical considerations. Understanding the pharmacology underlying the frequent co-abuse of MPH-ethanol provides rational guidance in the selection of first-line pharmacotherapy for comorbid ADHD-alcohol use disorder.
Objectives
Medication management of neurologic disorders can present challenges in an ambulatory care setting. Clinical pharmacy specialists (CPSs) may be uniquely positioned to assist with the medication adjustments and monitoring that is often necessary for these conditions. While pharmacist‐led clinics are well established in some areas of ambulatory care, few examples have been described within neurology. This project aims to describe the interventions associated with a pharmacist‐led neurology clinic within a Veterans Affairs (VA) Medical Center.
Methods
A pharmacist‐led neurology clinic was implemented to assist with medication management of various neurologic conditions and increase access to the neurology service. This retrospective chart review included patients referred to the CPS clinic during a 6‐month period, with a minimum follow‐up of 3 months. The number of medication changes, nonpharmacologic interventions, and adverse drug events (ADEs) managed by the CPS was determined. The number of interim pharmacist‐led visits was used as an estimate of neurology provider time saved.
Results
One hundred sixty‐four patients were included in the analyses. During the 9‐month period assessed, patients had a total of 307 visits in the pharmacist‐led neurology clinic. Patients were referred for multiple neurologic conditions, with headache, neuropathy, Parkinson's disease, non‐Parkinson's tremor, and seizure disorders being the most common. The CPS made 175 dose adjustments, 139 medication additions or discontinuations, and 135 nonpharmacologic interventions. In addition, 41 ADEs were identified and/or managed during CPS encounters. Patients had an average of two visits with the CPS in between scheduled neurology clinic appointments; this allowed for an estimated 34 appointment slots/month to remain open in the neurology provider clinics.
Conclusions
The implementation of a pharmacist‐led neurology clinic allowed for CPS management of medications for multiple neurologic conditions, including the management of ADEs, and increased access to the neurology ambulatory care service at this VA facility.
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