Pharmacokinetics and pharmacodynamics of hydroxychloroquine in hospitalized patients with COVID-19

Hydroxychloroquine (HCQ) dosage required to reach circulating levels that inhibit SARS-Cov-2 are extrapolated from pharmacokinetic data in non-COVID-19 patients. We performed a population-pharmacokinetic analysis 104 consecutive COVID-19 hospitalized patients (31 intensive care units, 73 medical wards, n = 149 samples). Plasma HCQ concentration were measured using high performance liquid chromatography with fluorometric detection. Modelling used Monolix-2019R2. doses ranged 200 800 mg/day administered for 1 11 days and median plasma was 151 ng/mL. Among the tested covariates, only bodyweight influenced elimination oral clearance (CL) apparent volume of distribution (Vd). CL/F (F unknown bioavailability) Vd/F (relative standard-error, %) estimates 45.9 L/h (21.2) 6690 L (16.1). The derived half-life (t1/2) 102 h. These parameters differed those reported lupus, where CL/F, t1/2 be 68 L/h, 2440 19.5 h, respectively. Within 72 h initiation, 16/104 (15.4%) had above vitro half maximal effective against SARS-CoV-2 (240 ng/mL). did not influence inflammation status (assessed by C-reactive protein) or viral real-time reverse transcription-PCR nasopharyngeal swabs). interindividual variability severe important previously Loading 1600 mg followed 600 daily needed concentrations relevant inhibition within hours ≥ 60% (95% confidence interval: 49.5–69.0%)