Serum albumin concentration: a predictive factor of infliximab pharmacokinetics
and clinical response in patients with ulcerative colitis.
Author(s): Fasanmade AA, Adedokun OJ, Olson A, Strauss R, Davis HM.
Affiliation(s): Pharmacokinetics, Modeling & Simulation, Clinical Pharmacology Sciences, Centocor
Research and Development, Inc., 200 Great Valley Parkway, Malvern, PA 19355, USA.
adedigbo@hotmail.com
Publication date & source: 2010, Int J Clin Pharmacol Ther. , 48(5):297-308
OBJECTIVES: Infliximab, an IgG1 monoclonal antibody (mab), has large
inter-individual serum concentration variability. The objective was to determine
the extent of the association of baseline albumin concentration and infliximab
disposition in patient with ulcerative colitis.
METHOD: Data from 728 patients with ulcerative colitis from two clinical trials
were analyzed to evaluate trends between infliximab pharmacokinetics and serum
albumin, or liver or kidney function. Response in the placebo and treated groups
were compared by baseline serum albumin concentrations (SAC) groups.
RESULTS: Patients with higher SAC maintained higher infliximab concentrations,
lower clearance, and longer half-life than patients with lower SAC. When analyzed
by SAC quartiles, patients in the highest quartile had several-fold greater
trough infliximab concentrations when compared with those in the lowest quartile.
These observations were consistent in both studies and at different dose levels.
Generally, clinical response in patients did not vary with SAC when the SAC was
within the normal range, apparently because serum infliximab concentrations
remained at therapeutic levels. However, patients with SAC lower than the normal
laboratory reference range had much lower median serum infliximab concentrations
and lower response rates compared with patients within normal SAC. Infliximab
pharmacokinetics did not correlate with SGOT or creatinine clearance.
CONCLUSIONS: It is hypothesized that the common rescue pathway for both albumin
and IgG involving the neonatal Fc receptor may be responsible for the
relationship between serum albumin and serum infliximab levels. Baseline albumin
level may serve as a valuable and convenient measure of mab pharmacokinetic
expectations in these patients.
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