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Pharmacokinetics and Protein Binding of Eprosartan in Hemodialysis‐Dependent Patients with End‐Stage Renal Disease
Author(s) -
Kovacs Steven J.,
Tenero David M.,
Martin David E.,
Ilson Bernard E.,
Jorkasky Diane K.
Publication year - 1999
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.19.8.612.31518
Subject(s) - hemodialysis , pharmacokinetics , medicine , dialysis , end stage renal disease , urology , renal function , gastroenterology
Study Objectives . To compare eprosartan pharmacokinetics in hemodialysis patients and in volunteers with normal renal function, and to determine the effect of hemodialysis on these values. Design . Open‐label, parallel‐group, single‐dose study. Setting . Outpatient hemodialysis treatment center and an industry‐affiliated clinical pharmacology unit. Patients . Ten healthy volunteers and nine hemodialysis patients. Intervention . A single oral dose of eprosartan 400 mg was administered to volunteers on 1 day and to patients on 2 days (a nondialysis and a dialysis day). Patients underwent high‐flux hemodialysis. Measurements and Main Results . Concentrations of eprosartan in plasma and dialysate were assayed by high‐performance liquid chromatography; plasma protein binding was determined by ultrafiltration. Eprosartan pharmacokinetics showed greater variability in patients than in volunteers. However, six of nine patients had exposures that were within the range observed for volunteers. Mean total AUC 0–t was increased approximately 60% (95% CI −22, 225) in patients. Total C max was similar between groups (PE = 1.01, 95% CI −40, 71). Mean percent fraction unbound (%f u ) in patients (3.02%) was significantly greater than that in volunteers (1.74%). Unbound AUC 0–t and unbound C max were, on average, approximately 172% (95% CI 28, 479) and 73% (95% CI −1, 199) greater, respectively, in patients. After hemodialysis, the mean %f u decreased from 3.19–2.01%. Mean recovery of eprosartan in dialysate was 6.8 mg (range 0–23.1 mg) and hemodialytic clearance was approximately 11 ml/minute, which does not represent a significant portion of total clearance. Conclusions . Eprosartan was safe and well tolerated in both groups. Based on its known safety profile and because of its exaggerated pharmacokinetic variability in patients undergoing hemodialysis, treatment should be individualized based on tolerability and response. Supplemental doses of eprosartan after hemodialysis are unnecessary.