Pharmacokinetics and protein binding of eprosartan in healthy volunteers and in patients with varying degrees of renal impairment.
This was an open-label, parallel group study to compare the pharmacokinetics of multiple oral doses of eprosartan in subjects with normal renal function (Clcr > 80 mL/min; n = 8) and patients with mild (Clcr 60-80 mL/min; n = 8), moderate (Clcr 30-59 mL/min; n = 15), or severe (Clcr < 30 mL/min; n = 3) renal insufficiency. Each subject received oral eprosartan 200 mg twice daily for 6 days and a single dose on day 7. Mean total maximum concentration (Cmax) and area under the concentration-time curve from 0 to 12 hours (AUC0-12) were similar for healthy subjects and those with mild renal impairment, but were an average of 25% to 35% and 51% to 55% greater for patients with moderate and severe renal impairment, respectively, compared with healthy subjects. Mean renal clearance (Clr), which was similar for healthy subjects and patients with mild renal impairment, was decreased an average of 41% and 95% in the groups with moderate and severe renal impairment, respectively, compared with normal subjects. Eprosartan was highly bound to plasma proteins in all groups; however, the unbound fraction was increased approximately two-fold in the group with severe renal impairment. Mean unbound Cmax and AUC0-12 were an average of 53% to 61% and 185% to 210% greater for the patients with moderate and severe renal impairment, respectively, compared with healthy subjects. Headache was the most common adverse experience reported in all subgroups. Eprosartan was safe and well tolerated regardless of degree of renal impairment. Cmax and AUC were increased and renal clearance decreased in patients with moderate to severe renal impairment in comparison to healthy subjects and patients with mild renal impairment. However, based on the moderate renal clearance and known safety profile of eprosartan, it is not necessary to adjust the dose of eprosartan in patients with renal insufficiency.
Martin
D E
DE
SmithKline Beecham Pharmaceuticals, Clinical Pharmacology Unit, Presbyterian Medical Center, University of Pennsylvania Health Care System, Philadelphia 19104, USA.
Chapelsky
M C
MC
Ilson
B
B
Tenero
D
D
Boike
S C
SC
Zariffa
N
N
Jorkasky
D K
DK
D000179:Acrylates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D051437:Renal Insufficiency / Q000097:blood / Q000378:metabolism*; D013876:Thiophenes
D000179:Acrylates; D000959:Antihypertensive Agents; D007093:Imidazoles; D013876:Thiophenes; C068373:eprosartan