A number of herbal preparations have been shown to interact with prescription medications secondary to modulation of cytochrome P450 (CYP) and/or P-glycoprotein (P-gp). The purpose of this study was to determine the influence of Panax ginseng on CYP3A and P-gp function using the probe substrates midazolam and fexofenadine, respectively. Twelve healthy subjects (8 males) completed this open label, single sequence pharmacokinetic study. Healthy volunteers received single oral doses of midazolam 8 mg and fexofenadine 120 mg, before and after 28 days of P. ginseng 500 mg twice daily. Midazolam and fexofenadine pharmacokinetic parameter values were calculated and compared pre-and post P. ginseng administration. Geometric mean ratios (post-ginseng/pre-ginseng) for midazolam area under the concentration vs. time curve from zero to infinity (AUC0-∞), half life (T1/2), and maximum concentration (Cmax) were significantly reduced at 0.66 (0.55 – 0.78), 0.71 (0.53 – 0.90), and 0.74 (0.56 – 0.93), respectively. Conversely, fexofenadine pharmacokinetics were unaltered by P. ginseng administration. Based on these results, Panax ginseng appeared to induce CYP3A activity in the liver and possibly the gastrointestinal tract. Patients taking Panax ginseng in combination with CYP3A substrates with narrow therapeutic ranges should be monitored closely for adequate therapeutic response to the substrate medication.

Study Objective To determine the influence of Echinacea purpurea on the pharmacokinetics of lopinavir-ritonavir, and on CYP3A and P-glycoprotein (P-gp) activity using the probe substrates midazolam, and fexofenadine, respectively. Design Open label, single-sequence pharmacokinetic study. Setting Outpatient clinic in a Federal Government research hospital. Subjects Thirteen (8 males) healthy volunteers (median age: 31 yrs). Measurements and main results Healthy volunteers received lopinavir-ritonavir (400/100 mg) twice daily for 30 days. On study day 16, subjects began taking Echinacea purpurea 500 mg three times daily, which they continued for four weeks, the first two weeks in combination with lopinavir-ritonavir. On days 15 and 30 of lopinavir-ritonavir administration (pre and post-Echinacea, respectively), serial blood samples were collected over 12 hrs to determine lopinavir and ritonavir concentrations and subsequent pharmacokinetic parameters using non-compartmental methods. Study subjects also received single doses of midazolam (8 mg orally) and fexofenadine (120 mg orally) before- and after 28 days of Echinacea purpurea to assess CYP3A and P-glycoprotein (P-gp) activity, respectively. Neither lopinavir nor ritonavir pharmacokinetics were significantly altered by 2 weeks of Echinacea coadministration. The geometric mean ratios (GMR, 90% CI) for lopinavir area under the concentration vs. time curve from zero to 12 hrs (AUC0–12) and maximum concentration (post-Echinacea/pre-Echinacea) were 0.96 (0.83, 1.10) and 1.00 (0.88, 1.12), respectively (P > 0.05). Conversely, GMRs (90% CIs) for midazolam AUC from time zero to infinity (AUC0-∞) and oral clearance were 0.73 (0.61, 0.85) (P = 0.008) and 1.37 (1.10, 1.63) (P = 0.02), respectively. Fexofenadine pharmacokinetics did not significantly differ pre- and post-echinacea administration (P > 0.05). Conclusion Echinacea purpurea induced CYP3A activity but did not alter lopinavir concentrations, most likely due to the presence of the potent CYP3A inhibitor, ritonavir. Echinacea purpurea is unlikely to alter the pharmacokinetics of ritonavir-boosted protease inhibitors but may cause modest decreases in plasma concentrations of other CYP3A substrates.

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Introduction Despite a significant reduction in mother‐to‐child transmission of HIV, an estimated 180,000 children were infected with HIV in 2017, and only 52% of children under 15 years of age living with HIV (CLHIV) are on life‐saving antiretroviral therapy (ART). Without effective treatment, half of CLHIV die before the age of two years and only one in five survives to five years of age. Discussion Over the past four years, the United States Food and Drug Administration tentatively approved new formulations of lopinavir/ritonavir (LPV/r) in the form of oral pellets and oral granules. However, the slow uptake of the aforementioned formulations in the low‐ and middle‐income countries with the highest paediatric HIV burden is largely due to three challenges: limited manufacturing capacity; current unit cost of the pellets and granules; and slow uptake of these new formulations by policy makers and health care workers. Conclusions Solutions to overcome these barriers include ensuring availability of an adequate supply of LPV/r oral pellets and oral granules, considering all programmatic and clinical factors when selecting paediatric ART formulations, and leveraging current resources to decrease paediatric HIV morbidity and mortality.

Study Objective As we previously observed a significant 41% reduction in gemfibrozil exposure after 2 weeks of lopinavir-ritonavir administration, we sought to determine the influence of lopinavir-ritonavir and ritonavir alone on the pharmacokinetics of fenofibric acid, an alternative to gemfibrozil for the treatment of elevated triglyceride levels. Design Open-label, single-sequence pharmacokinetic study. Setting Clinical Research Center at the National Institutes of Health. Subjects Thirteen healthy adult volunteers. Intervention Subjects received a single oral dose of fenofibrate 145 mg during three study phases: before ritonavir administration, after 2 weeks of administration of ritonavir 100 mg twice daily, and after 2 weeks of administration of lopinavir 400 mg–ritonavir 100 mg twice daily. Measurements and Main Results Serial blood samples were collected over 120 hours for determination of fenofibric acid concentrations. Fenofibric acid pharmacokinetic parameter values were compared before and after concomitant ritonavir or lopinavir-ritonavir administration. The geometric mean ratios (90% confidence intervals) for fenofibric acid area under the plasma concentration–time curve were 0.89 (0.77–1.01) after 14 days of ritonavir alone compared with baseline (p>0.05) and 0.87 (0.69–1.05) after 14 days of lopinavir-ritonavir compared with baseline (p>0.05). Study drugs were generally well tolerated; all adverse events were mild or moderate, transient, and resolved without intervention. Conclusion In contrast to a significant interaction between gemfibrozil and lopinavir-ritonavir, neither lopinavir-ritonavir nor ritonavir alone altered the pharmacokinetics of fenofibric acid in healthy volunteers. These data suggest that fenofibrate remains an important option in human immunodeficiency virus–infected patients receiving common ritonavir-boosted therapy.

The United States President's Emergency Plan for AIDS Relief (PEPFAR) is the largest commitment by any nation to combat a single disease through prevention and treatment initiatives; pharmacists play a critical role in improving the accessibility of antiretrovirals (ARVs). When determining the potential use of a medication for a human immunodeficiency virus (HIV) program, it is helpful to consider decisions through the (a) Perspective of a patient, (b) Perspective of the overarching HIV program providing care, and (c) Perspective of the ARV market. Pharmacists are uniquely positioned to contribute to decisions from these three perspectives. At the beginning of PEPFAR, the price of ARVs was cost prohibitive; however, after 17 years since its inception, through the work of pharmacists and other public health professionals, the price to treat one patient for one year is currently 63 USD. This article describes the impact of pharmacists at the U.S. Agency for International Development (USAID) and the Food and Drug Administration (FDA) in facilitating a dramatic reduction in the cost of ARVs, through the use of an expedited approval process and through pooling procurement of ARVs from a limited formulary.

Extensive planning and accounting for supply chain factors is essential to ensuring a smooth transition to a new regimen and to enable the global antiretroviral market to respond adequately.

Health disparities exist globally in high‐income and low‐ and middle‐income countries. They are driven by social determinants of health (SDOH). While a role for pharmacists in addressing SDOH exists, a lack of structured postgraduate training limits pharmacists from being equipped to build innovative programs and contribute to health policy on SDOH in an impactful way. Postgraduate training, specifically, fellowships provides opportunities for pharmacists to develop the needed skills for working with SDOH. The Purdue University College of Pharmacy (PUCOP)‐United States Agency for International Development (USAID) Global Health Equity Fellowship was developed to meet this training need. This 2‐y fellowship represents a partnership between USAID and PUCOP. During the fellowship, time is split between USAID in Washington DC, PUCOP in Indianapolis, Indiana, and the Purdue Kenya Partnership (PKP) in Eldoret, Kenya. The fellowship was developed with a foundation of core values, the creation of a logic model, strategic partnerships, maintaining an adaptable structure, and intentional partner communication. Fellow outcomes were evaluated in three categories: engagement, education, and scholarship. Fellows completed 10 experiential opportunities between three sites and participated in the development of new and supported ongoing care programs and policy implementation in both local and international settings. Fellows completed the following educational outcomes: completed an online Master of Public Health (MPH) through Purdue Global, provided 13 educational presentations and lectures at various sites, and precepted a total of 12 PUCOP advanced pharmacy practice experience (APPE) students and 16 Kenyan pharmacy interns and Master of Pharmacy (MPharm) students. Fellows completed three publications and two abstracts at international conferences. This established training model provides pharmacists with a structured path to gain the knowledge, skills, and attitudes to be leaders in addressing Global Health Equity.