Population pharmacokinetics of brodalumab in patients with moderate to severe plaque psoriasis.

Abstract:

:Brodalumab is a fully human monoclonal antibody targeting the IL-17 receptor A leading to an inhibition of the biological effect of IL-17A, IL-17F, IL-17A/F heterodimer, IL-17C and IL-17E isoforms. It has shown to be efficacious in the treatment of moderate to severe plaque psoriasis (210 mg administered subcutaneously at weeks 0, 1 and 2 followed by 210 mg every 2 weeks [Q2W+1]). A population pharmacokinetic model based on psoriasis patients only from six clinical trials was developed to describe the pharmacokinetics and identify sources of variability. In patients with psoriasis, Brodalumab exhibits non-linear pharmacokinetics due to target-mediated drug disposition resulting in concentration-dependent clearance. The pharmacokinetics was best described by a two-compartment model with linear absorption and combined linear and Michaelis-Menten elimination. The subcutaneous bioavailability of Brodalumab was 55%, absorption rate was 0.30 day-1 , and body-weight was found to affect the volume of distribution and clearance. For a reference patient with plaque psoriasis (body-weight of 90 kg), the estimates were 0.16 L/d for linear serum clearance, 6.1 mg/d for the maximum non-linear clearance rate, and 4.7 and 2.4 L for central and peripheral volume of distribution, respectively. For the approved dosing regimen, time to maximum concentration was 4 days and 90% of steady-state was achieved after 10 weeks for a reference patient. Following last dose at steady-state, 90% of the population of reference patients will reach serum concentrations below lower limit of quantification after 45 days.

authors

Timmermann S,Hall A

doi

10.1111/bcpt.13202

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

16-25

issue

1

eissn

1742-7835

issn

1742-7843

journal_volume

125

pub_type

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