Clinical pharmacokinetics of kavalactones after oral dosing of standardized kava extract in healthy volunteers.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper methysticum G. Forst. (Piperaceae), commonly known as kava, has been used as a traditional beverage for centuries for its relaxing properties. Kavalactones are considered to be the major constituents responsible for kava's beneficial effects. Despite the extensive use of kava, clinical pharmacokinetic data is not available in the literature; therefore, the findings of this study will be critical for the dosage calculations for future clinical evaluation of kava. AIM OF THE STUDY: The aim of the current study is to examine the clinical pharmacokinetics of six major kavalactones following oral dosing of flavokavain A/B-free standardized kava extract capsules in healthy volunteers using two dosage regimens. MATERIALS AND METHODS: A sensitive, reliable, and specific ultra-high pressure liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous quantification of six major kavalactones (kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin) and two flavokavains (A and B) in human plasma. Pharmacokinetic profiles were assessed in ten healthy volunteers after oral doses of standardized kava product, and plasma samples were analyzed for six kavalactones and two flavokavains using the validated UPLC-MS/MS method. Concentration-time data was subjected to pharmacokinetic analysis. RESULTS: The systemic exposure of the kavalactones was found to be in the following order: dihydrokavain > dihydromethysticin > kavain > methysticin > yangonin. Desmethoxyyangonin was quantifiable only at a couple of time points, while flavokavain A and flavokavain B were not present in any of the plasma samples. Fast absorption of five kavalactones was observed with time to reach the maximum plasma concentration of 1-3 h. A dose proportionality in pharmacokinetics was established from 75 to 225 mg of kavalactone doses. In the multiple-dose study, a significant reduction in the extent of absorption of kavalactones with food was observed. CONCLUSION: Single and multiple-dose clinical pharmacokinetic studies for kava were performed in healthy volunteers, and higher exposure to the kavalactones was observed after single-dosing (225 mg), while a longer duration of exposure was observed after three times a day (3 x 75 mg) dosing.

Building coalitions: A statewide nursing organization's role in changing nursing education regulation during the COVID-19 pandemic.

The California Association of Colleges of Nursing (CACN), representing California's baccalaureate and higher degree nursing education programs, has raised concerns for over two-years about the number, relevance, and legitimacy of nursing education regulations. Formal CACN letters to state regulators did not affect change. While California nursing education regulations require 75% direct patient contact for all clinical courses, meeting this requirement became impossible as clinical agencies closed to nursing students during the beginning of the COVID-19 pandemic. Nursing regulatory change was urgently needed to provide greater flexibility in meeting clinical course objectives using simulation and other online learning modalities. At stake was the graduation of over 14,971 RN students from public and private nursing programs. While state regulators opposed a legislative approach, CACN collaborated with stakeholders to support legislation that led to a reduction in direct patient care hours, allowing nursing students to progress and graduate. This longstanding advocacy work was accelerated by the pandemic and required leadership and knowledge about the legislative process for nurse educators to succeed. The ultimate goal for CACN is to forge a more respectful relationship and greater collaboration between educators and regulators to enhance quality, reduce costs, and redundancies in nursing education in this state.

Acceptability, Feasibility, and Utility of Integrating Pharmacogenetic Testing into a Child Psychiatry Clinic.

Pharmacogenetic (PGx) testing is a tool to identify patients at a higher risk of adverse events or treatment failure. The concern for unwanted side effects can limit medication adherence, particularly in children and adolescents. We conducted a pragmatic study to evaluate the acceptability and feasibility and gather pilot data on the utility of PGx testing in a child and adolescent psychiatry clinic. Both physicians and families participated in the study and answered pre-survey and post-survey questionnaires to examine their attitudes toward PGx testing. Patients were randomized into implementation (N = 25) and control groups (N = 24) and underwent PGx testing at the beginning or end of the study, respectively. Clinical consult notes with genotype-guided recommendations were provided to physicians for their consideration in clinical decisions. Patient-reported symptom severity and antidepressant-related side effects were assessed at baseline and for 12 weeks. Both participating physicians and families agreed that PGx testing is a useful tool to improve medication selection. The time from sample collection to having PGx test results was ~ 10 days and 15 days to having consult notes available, which may have impaired test utility in clinical decision making. There were no differences in any clinical end point between the implementation and control arms; however, there were higher antidepressant side effect scores for CYP2D6 poor and intermediate metabolizers after the eighth week of treatment. Our findings revealed benefits and pitfalls with the use of PGx testing in the real-world clinical setting, which may inform the methodology of a larger trial focused on outcomes.