Secondary Logo

Institutional members access full text with Ovid®

Share this article on:

A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients

Klaasen, Rolf Anton, MScPharm*,†; Egeland, Erlend Johannessen, MScPharm; Chan, Joe, MD§; Midtvedt, Karsten, MD, PhD; Svensson, My, MD, PhD§; Bolstad, Nils, MD*; Fellström, Bengt, MD, PhD; Holdaas, Hallvard, MD, PhD; Åsberg, Anders, PhD; Bergan, Stein, PhD; Vethe, Nils Tore, PhD; Warren, David John, PhD*

doi: 10.1097/FTD.0000000000000580
Original Article

Background: Belatacept (Nulojix; Bristol-Myers Squibb, New York, NY) is a biological immunosuppressive drug used for the prophylaxis of acute rejection after renal transplantation. Few studies have described belatacept pharmacokinetics, and the effect of therapeutic drug monitoring has not been investigated. We have developed a drug-capture assay (using drug target) to measure belatacept in serum and applied this assay in a pharmacokinetic study in renal transplant recipients.

Methods: CD80 was used to trap belatacept onto streptavidin-coated wells. Captured drug was quantified using Eu3+-labeled protein A and time-resolved fluorescence. The assay was applied in a pilot pharmacokinetic study in renal transplanted patients receiving belatacept infusions. Belatacept serum concentrations were determined at several time points between belatacept infusions. A simple population pharmacokinetic model was developed to visualize measured and predicted belatacept serum concentrations.

Results: The assay range was 0.9–30 mg/L with accuracy within 91%–99% and coefficients of variation ranging from 1.2% to 3.6%. Predilution extended the measurement range to 130 mg/L with an accuracy of 90% and coefficients of variation of 3.8%. Samples were stable during storage at 4°C for 15 days and during 2 freeze-thaw cycles. Belatacept concentrations were determined in a total of 203 serum samples collected during 26 infusion intervals from 5 renal transplant recipients. The population pharmacokinetic model visualized both measured and predicted concentrations.

Conclusions: We have developed an automated, accurate, and precise assay for the determination of belatacept serum concentrations. The assay was successfully applied in a pharmacokinetic study in renal transplant recipients receiving belatacept infusions.

Departments of *Medical Biochemistry, Radiumhospitalet and

Pharmacology, Rikshospitalet, Oslo University Hospital, Oslo;

Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo;

§Department of Renal Medicine, Akershus University Hospital, Lørenskog;

Department of Transplantation Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway; and

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Correspondence: Erlend Johannessen Egeland, MScPharm, Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Postbox 1068 Blindern, 0316 Oslo, Norway (e-mail: e.j.egeland@farmasi.uio.no).

R. A. Klaasen and E. J. Egeland contributed equally as first authors.

B. Fellström has received a grant from Bristol-Myers Squibb. The remaining authors declare no conflict of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.drug-monitoring.com).

Received August 27, 2018

Accepted October 11, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.