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Contribution of Renal and Non‐Renal Clearance on Increased Total Clearance of Adalimumab in Glomerular Disease
Author(s) -
Roberts Brittney V.,
Susano Isidro,
Gipson Debbie S.,
Trachtman Howard,
Joy Melanie S.
Publication year - 2013
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/jcph.121
Subject(s) - renal function , clearance , urology , proteinuria , urine , adalimumab , chemistry , medicine , endocrinology , focal segmental glomerulosclerosis , creatinine , nephrotic syndrome , kidney , disease
The contribution of renal and non‐renal clearance toward targeted concentrations and/or effects of therapeutic proteins in nephrotic patients are unknown. This study dissected the contribution of clearance pathways to adalimumab elimination in patients with focal segmental glomerulosclerosis (FSGS). Urine was collected from seven patients treated with adalimumab. Renal clearance (Cl R ) was measured and non‐renal clearance (Cl NR ) was calculated as the difference between total clearance and Cl R . Differences in cumulative amount in urine, Cl R , and Cl NR between study weeks 1 and 16 and relationships between proteinuria (protein:creatinine ratio (Up/c)), and Cl R and Cl NR were evaluated. Up to 13% of the adalimumab dose was lost in urine. Cl NR contributed more than Cl R to enhanced total clearance. There was a nonlinear relationship between Up/c and Cl R (R 2 0.7059); an increase in Cl R beginning at Up/c of 12 mg/mg [slope 1.755, (C.I. −7.825 to 11.34)]. There was a linear relationship between Up/c and Cl NR (R 2 0.5039); for every one unit increase in Up/c, Cl NR would increase by 3.5 mL/hr ( P = 0.01). Both Cl R and Cl NR contribute to enhanced total clearance of adalimumab in glomerular disease secondary to FSGS. Additional research is needed to identify mechanisms for the increased Cl NR pathways.