Abstract
Inflammation is strongly associated with malnutrition and cardiovascular risk in patients with chronic renal failure on haemodialysis (HD). The acute-phase inflammatory response, defined by the increased synthesis of positive acute-phase proteins, is stimulated by the production of such cytokines as interleukin 6 (IL-6), interleukin 1 (IL-1) and tumour necrosis factor-α TNF-α The availability of cytokine antagonists allows testing of the hypothesis that suppression of inflammation reverses the malnutrition-inflammation syndrome in HD patients. Etanercept is a soluble TNF-α receptor fusion protein used to suppress inflammation in rheumatoid and psoriatic arthritis. Its metabolism in HD patients is unknown. In a study designed to test the safety and pharmacokinetics of etanercept in HD patients, etanercept was administered to six HD patients with albumin levels above 4.2 g dL-1 and C-reactive protein levels <5 mg L-1 (five men, one woman, age range 34-59 years). Etanercept (25 mg) was administered subcutaneously twice weekly immediately after dialysis for 13-16 weeks. Etanercept concentrations were measured pre- and post-dialysis by ELISA. Concentrations were compared graphically to assess whether, firstly, dialysis affects etanercept apparent clearance and, secondly, etanercept kinetics were similar between HD patients and the more extensively studied psoriasis population with normal renal function (PS). The second stage examined model-based parameter predictions of the terminal elimination rate constant (k) for HD patients. Steady-state etanercept levels were comparable between HD and PS patients. Treatment with HD had no effect on etanercept levels. When etanercept was discontinued, the terminal rate constant for HD patients was not significantly different from that observed in PS patients. No adverse effects were noted during the 3-month treatment phase and subsequent 6-month follow-up. Albumin and C-reactive protein levels did not change in these non-inflamed patients during the study period. The pharmacokinetics of etanercept in patients with chronic renal failure on HD are similar to patients with normal renal function. It is, therefore, feasible to administer etanercept to HD patients without adjusting the dose
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1407-1413 |
| Number of pages | 7 |
| Journal | Journal of Pharmacy and Pharmacology |
| Volume | 57 |
| Issue number | 11 |
| DOIs | |
| State | Published - 2005 |
Fingerprint
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
Cite this
The pharmacokinetics of etanercept in patients with end-stage renal disease on haemodialysis. / Don, Burl R; Spin, Gregory; Nestorov, Ivan; Hutmacher, Matt; Rose, Aubri; Kaysen, George.
In: Journal of Pharmacy and Pharmacology, Vol. 57, No. 11, 2005, p. 1407-1413.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The pharmacokinetics of etanercept in patients with end-stage renal disease on haemodialysis
AU - Don, Burl R
AU - Spin, Gregory
AU - Nestorov, Ivan
AU - Hutmacher, Matt
AU - Rose, Aubri
AU - Kaysen, George
PY - 2005
Y1 - 2005
N2 - Inflammation is strongly associated with malnutrition and cardiovascular risk in patients with chronic renal failure on haemodialysis (HD). The acute-phase inflammatory response, defined by the increased synthesis of positive acute-phase proteins, is stimulated by the production of such cytokines as interleukin 6 (IL-6), interleukin 1 (IL-1) and tumour necrosis factor-α TNF-α The availability of cytokine antagonists allows testing of the hypothesis that suppression of inflammation reverses the malnutrition-inflammation syndrome in HD patients. Etanercept is a soluble TNF-α receptor fusion protein used to suppress inflammation in rheumatoid and psoriatic arthritis. Its metabolism in HD patients is unknown. In a study designed to test the safety and pharmacokinetics of etanercept in HD patients, etanercept was administered to six HD patients with albumin levels above 4.2 g dL-1 and C-reactive protein levels <5 mg L-1 (five men, one woman, age range 34-59 years). Etanercept (25 mg) was administered subcutaneously twice weekly immediately after dialysis for 13-16 weeks. Etanercept concentrations were measured pre- and post-dialysis by ELISA. Concentrations were compared graphically to assess whether, firstly, dialysis affects etanercept apparent clearance and, secondly, etanercept kinetics were similar between HD patients and the more extensively studied psoriasis population with normal renal function (PS). The second stage examined model-based parameter predictions of the terminal elimination rate constant (k) for HD patients. Steady-state etanercept levels were comparable between HD and PS patients. Treatment with HD had no effect on etanercept levels. When etanercept was discontinued, the terminal rate constant for HD patients was not significantly different from that observed in PS patients. No adverse effects were noted during the 3-month treatment phase and subsequent 6-month follow-up. Albumin and C-reactive protein levels did not change in these non-inflamed patients during the study period. The pharmacokinetics of etanercept in patients with chronic renal failure on HD are similar to patients with normal renal function. It is, therefore, feasible to administer etanercept to HD patients without adjusting the dose
AB - Inflammation is strongly associated with malnutrition and cardiovascular risk in patients with chronic renal failure on haemodialysis (HD). The acute-phase inflammatory response, defined by the increased synthesis of positive acute-phase proteins, is stimulated by the production of such cytokines as interleukin 6 (IL-6), interleukin 1 (IL-1) and tumour necrosis factor-α TNF-α The availability of cytokine antagonists allows testing of the hypothesis that suppression of inflammation reverses the malnutrition-inflammation syndrome in HD patients. Etanercept is a soluble TNF-α receptor fusion protein used to suppress inflammation in rheumatoid and psoriatic arthritis. Its metabolism in HD patients is unknown. In a study designed to test the safety and pharmacokinetics of etanercept in HD patients, etanercept was administered to six HD patients with albumin levels above 4.2 g dL-1 and C-reactive protein levels <5 mg L-1 (five men, one woman, age range 34-59 years). Etanercept (25 mg) was administered subcutaneously twice weekly immediately after dialysis for 13-16 weeks. Etanercept concentrations were measured pre- and post-dialysis by ELISA. Concentrations were compared graphically to assess whether, firstly, dialysis affects etanercept apparent clearance and, secondly, etanercept kinetics were similar between HD patients and the more extensively studied psoriasis population with normal renal function (PS). The second stage examined model-based parameter predictions of the terminal elimination rate constant (k) for HD patients. Steady-state etanercept levels were comparable between HD and PS patients. Treatment with HD had no effect on etanercept levels. When etanercept was discontinued, the terminal rate constant for HD patients was not significantly different from that observed in PS patients. No adverse effects were noted during the 3-month treatment phase and subsequent 6-month follow-up. Albumin and C-reactive protein levels did not change in these non-inflamed patients during the study period. The pharmacokinetics of etanercept in patients with chronic renal failure on HD are similar to patients with normal renal function. It is, therefore, feasible to administer etanercept to HD patients without adjusting the dose
UR - http://www.scopus.com/inward/record.url?scp=34548084289&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34548084289&partnerID=8YFLogxK
U2 - 10.1211/jpp.57.11.0005
DO - 10.1211/jpp.57.11.0005
M3 - Article
C2 - 16259772
AN - SCOPUS:34548084289
VL - 57
SP - 1407
EP - 1413
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 11
ER -