TY - JOUR
T1 - Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous Nephropathy
AU - Fogueri, Uma
AU - Cheungapasitporn, Wisit
AU - Bourne, David
AU - Fervenza, Fernando C.
AU - Joy, Melanie S.
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Fernando C Fervenza has received unrestricted research grants from Genentech- the maker of Rituximab.
Publisher Copyright:
© The Author(s) 2018.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Background: Rituximab (RTX) is a chimeric monoclonal anti-CD20 antibody used off-label in the treatment of membranous nephropathy (MN). Unfortunately, limited information is available on the pharmacokinetics of therapeutic proteins such as RTX in patients with glomerular kidney diseases. Objective: The current study evaluated RTX pharmacokinetics in patients with MN (n = 20) who received 4 RTX weekly intravenous infusions (375 mg/m 2 ) over a month, with a repeat of the identical treatment at 6 months. Baseline patient characteristics were gender (17 male/3 female), age (49 ± 13 years), and body surface area (2.2 ± 0.24 m 2 ). Methods: Compartmental pharmacokinetic analyses were conducted using Phoenix, and comparisons of these parameters were made between the MN patients and published data from 2 reference populations without kidney diseases (follicular lymphoma and autoimmune disorders). Results: Patients with MN exhibited a shorter half-life, reduced volume of central compartment, decreased area under the serum concentration-time curve (exposure), and increased RTX clearance from the central compartment versus previous reports in the reference patient populations. Conclusions and Relevance: These results suggest that shorter half-life and lower exposures to RTX in patients with MN may necessitate higher doses and/or changes to dosing frequency to optimize the relationships between serum concentrations and therapeutic effects.
AB - Background: Rituximab (RTX) is a chimeric monoclonal anti-CD20 antibody used off-label in the treatment of membranous nephropathy (MN). Unfortunately, limited information is available on the pharmacokinetics of therapeutic proteins such as RTX in patients with glomerular kidney diseases. Objective: The current study evaluated RTX pharmacokinetics in patients with MN (n = 20) who received 4 RTX weekly intravenous infusions (375 mg/m 2 ) over a month, with a repeat of the identical treatment at 6 months. Baseline patient characteristics were gender (17 male/3 female), age (49 ± 13 years), and body surface area (2.2 ± 0.24 m 2 ). Methods: Compartmental pharmacokinetic analyses were conducted using Phoenix, and comparisons of these parameters were made between the MN patients and published data from 2 reference populations without kidney diseases (follicular lymphoma and autoimmune disorders). Results: Patients with MN exhibited a shorter half-life, reduced volume of central compartment, decreased area under the serum concentration-time curve (exposure), and increased RTX clearance from the central compartment versus previous reports in the reference patient populations. Conclusions and Relevance: These results suggest that shorter half-life and lower exposures to RTX in patients with MN may necessitate higher doses and/or changes to dosing frequency to optimize the relationships between serum concentrations and therapeutic effects.
KW - clearance
KW - membranous nephropathy
KW - monoclonal antibody
KW - pharmacokinetics
KW - rituximab
UR - http://www.scopus.com/inward/record.url?scp=85060327708&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85060327708&partnerID=8YFLogxK
U2 - 10.1177/1060028018803587
DO - 10.1177/1060028018803587
M3 - Article
C2 - 30293439
AN - SCOPUS:85060327708
SN - 1060-0280
VL - 53
SP - 357
EP - 363
JO - Annals of Pharmacotherapy
JF - Annals of Pharmacotherapy
IS - 4
ER -