Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Dec 2020
ReviewPharmacokinetics and Pharmacological Properties of Chloroquine and Hydroxychloroquine in the Context of COVID-19 Infection.
Chloroquine and hydroxychloroquine are quinoline derivatives used to treat malaria. To date, these medications are not approved for the treatment of viral infections, and there are no well-controlled, prospective, randomized clinical studies or evidence to support their use in patients with coronavirus disease 2019 (COVID-19). ⋯ This work provides basic clinical pharmacology information relevant for planning and initiating COVID-19 clinical studies with chloroquine or hydroxychloroquine, summarizes safety data from healthy volunteer studies, and summarizes safety data from phase II and phase II/III clinical studies in patients with uncomplicated malaria, including a phase II/III study in pediatric patients following administration of azithromycin and chloroquine in combination. In addition, this work presents data describing the proposed mechanisms of action against the severe acute respiratory distress syndrome coronavirus-2 and summarizes clinical efficacy to date.
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Clin. Pharmacol. Ther. · Oct 2020
Finding the dose for hydroxychloroquine prophylaxis for COVID-19; the desperate search for effectiveness.
Hydroxychloroquine is an antimalarial drug being tested as a potential treatment for the novel coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2. Although the efficacy of hydroxychloroquine for COVID-19 remains uncertain, it may serve as a potential prophylactic agent especially in those at high risk, such as healthcare workers, household contacts of infected patients, and the immunocompromised. ⋯ In an exposure driven, post-exposure prophylaxis setting, 800 mg loading dose followed in 6 hours by 600 mg, then 600 mg daily for 4 more days achieved daily troughs above EC50 in > 50% subjects. These doses are higher than recommended for malaria chemoprophylaxis, and clinical trials are needed to establish safety and efficacy.
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Clin. Pharmacol. Ther. · Oct 2020
ReviewChallenges in Drug Development Posed by the COVID-19 Pandemic: An Opportunity for Clinical Pharmacology.
The unprecedented challenges posed by the coronavirus disease 2019 (COVID-19) pandemic highlight the urgency for applying clinical pharmacology and model-informed drug development in (i) dosage optimization for COVID-19 therapies, (ii) approaching therapeutic dilemmas in clinical trial settings, and (iii) maximizing value of information from impacted non-COVID-19 trials. More than ever, we have a responsibility for adaptive evidence synthesis with a Totality of Evidence mindset in this race against time across biomedical research, clinical practice, drug development, and regulation.
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Clin. Pharmacol. Ther. · Sep 2020
ReviewCan a Multistakeholder Prioritization Structure Support Regulatory Decision Making? A Review of Pediatric Oncology Strategy Forums Reflecting on Challenges and Opportunities of this Concept.
Timely and successful drug development for rare cancer populations, such as pediatric oncology, requires consolidated efforts in the spirit of shared responsibility. In order to advance tailored development efforts, the concept of multistakeholder Strategy Forum involving industry, academia, patient organizations, and regulators has been developed. In this study, we review the first five pediatric oncology Strategy Forums co-organized by the European Medicines Agency between 2017 and 2020, reflecting on the outcomes and the evolution of the concept over time and providing an outline of how a "safe space" for multistakeholder engagement facilitated by regulators could be of potential value beyond pediatric oncology drug development.