Clinical pharmacokinetics of etanercept

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Clinical pharmacokinetics of etanercept: a fully humanized soluble

recombinant tumor necrosis factor receptor fusion protein.

J Clin Pharmacol. 2005 May;45(5):490-7.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=pubmed & dopt=Abstra\

ct & list_uids=15831771

Zhou H.

Clinical Pharmacology, Wyeth Pharmaceuticals, Collegeville, PA 19426.

Etanercept, a fully humanized soluble recombinant tumor necrosis factor

receptor fusion protein, is an approved treatment for rheumatoid arthritis,

juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis,

and psoriasis.

Etanercept is absorbed slowly from the site of subcutaneous

injection, with time to peak concentration at approximately 48 to 60 hours,

and is cleared slowly from the body with a t(1/2) of 70 to 100 hours. The

absolute bioavailability of etanercept was 58% in healthy subjects following

subcutaneous administration.

The 25-mg twice-weekly dosage regimen generates

systemic exposures comparable to 50 mg once weekly, as predicted by

pharmacokinetic modeling and simulation and later confirmed by clinical

studies.

The pharmacokinetics of etanercept in patients with rheumatoid

arthritis are comparable to those in healthy individuals and patients with

ankylosing spondylitis, congestive heart failure, and psoriasis.

In children

with polyarticular-course juvenile rheumatoid arthritis, after subcutaneous

doses of 0.4 mg/kg twice weekly, the clearance of etanercept may be slightly

reduced in children aged 4 to 8 years. Pharmacokinetic simulation predicts

that a dose of 0.8 mg/kg once weekly generates comparable systemic exposure

as 0.4 mg/kg twice weekly.

No requirement for etanercept dosage adjustment

is needed when etanercept is coadministered with warfarin, digoxin, or

methotrexate.

PMID: 15831771 [PubMed - in process]