Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous Nephropathy.
Ann Pharmacother
; 53(4): 357-363, 2019 04.
Article
in En
| MEDLINE
| ID: mdl-30293439
ABSTRACT
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/m2) 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 m2).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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Glomerulonephritis, Membranous
/
Rituximab
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Ann Pharmacother
Journal subject:
FARMACOLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2019
Document type:
Article
Affiliation country:
United States