@article{2a31931d548d4bf29225a5db6d2d91ce,
title = "A Pharmacokinetics-Informed Approach to Navigating Hydroxychloroquine Shortages in Patients With Rheumatic Disease During the COVID-19 Pandemic",
abstract = "Objective: The recent hydroxychloroquine (HCQ) shortage due to use in coronavirus disease 2019 (COVID-19) has forced some rheumatic disease patients to choose between continuing their current dose of HCQ but exhaust their supply early or ration it in order to prolong its use. Blood HCQ concentrations are directly correlated with disease activity in rheumatic diseases such as systemic lupus erythematosus. We sought to model how changes in HCQ dosage will best maintain sufficient blood HCQ concentrations for the longest period of time in order to avoid potential future flares. Methods: A one-compartment pharmacokinetic model was used to predict mean blood HCQ concentrations. Monte Carlo simulations with 10-fold inflated model parameter variance was utilized to assess the impact of variability. Results: Maintenance of 400 mg/d resulted in mean therapeutic whole-blood HCQ concentrations that exceeded 700 ng/ml for 10.5 days, whereas HCQ rationing by reducing the dose by half resulted in the mean concentration remaining above 700 ng/ml for 2.4 days (net gain = 8 days). Variability analysis demonstrates that results may differ at the individual level, dependent on baseline blood HCQ concentrations. Conclusion: Although mean blood concentrations exceed 700 ng/ml for a longer time if patients maintain their full dose of HCQ, more information is needed to fully understand the elimination of HCQ at the patient level, particularly the contribution of tissue stores of HCQ transiting back into the blood.",
author = "Scheetz, {Marc H.} and Konig, {Maximilian F.} and Robinson, {Philip C.} and Sparks, {Jeffrey A.} and Kim, {Alfred H.J.}",
note = "Funding Information: The authors have no disclosures to report where potential benefit (including finanacial) or harm due to publication of this manuscript. MHS outside of this work is supported by NIH National Institute of Allergy and Infectious Disease (NIAID) (R21-AI-149026, K24-AI-104831, R01-AI-119446), Cystic Fibrosis Foundation, Nevakar, Allecra, and Merck (less than $10,000 each). PCR reports no competing interests related to this work, outside of this work he reports personal consulting fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB (less than $10,000 each) and nonfinancial support from BMS and Roche. MFK outside of this work is supported by NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) T32-AR-048522 and reports personal fees unrelated to this work from Bristol-Myers Squibb and Celltrion (less than $10,000 each). JAS reports outside of this work is supported by NIH NIAMS/NIAID/Autoimmune Centers of Excellence, the Rheumatology Research Foundation, the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund as well as personal fees unrelated to this work from Bristol-Myers Squibb, Gilead, Inova, Janssen, and Optum (less than $10,000 each). AHJK reports outside of this work is supported by NIH NIAMS P30-AR-073752, Rheumatology Research Foundation, and GlaxoSmithKline, along with personal fees from Exagen Diagnostics, Inc. and GlaxoSmithKline (less than $10,000 each). Publisher Copyright: {\textcopyright} 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.",
year = "2020",
month = aug,
day = "1",
doi = "10.1002/acr2.11164",
language = "English",
volume = "2",
pages = "491--495",
journal = "ACR Open Rheumatology",
issn = "2578-5745",
number = "8",
}