Premium
Population Pharmacokinetics of Eniporide and Its Metabolite in Healthy Subjects and Patients With Acute Myocardial Infarction
Author(s) -
Bhattaram Venkatesh Atul,
Nagaraja Nelamangala V.,
Peters Tanja,
Machnig Thomas,
Kroesser Sonja,
Kovar Andreas,
Derendorf Hartmut
Publication year - 2005
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 - 10.1177/0091270004274431
Subject(s) - pharmacokinetics , medicine , volume of distribution , metabolite , population , myocardial infarction , population pharmacokinetics , creatinine , pharmacology , environmental health
Eniporide (EMD 96 875) is a novel and selective inhibitor of the Na + ‐H + exchange (NHE‐1) inhibitor. The study objectives were to identify a structural model for population pharmacokinetic analysis of eniporide and its metabolite (EMD 112 843) using nonlinear mixed‐effects modeling after short‐term infusion (dose: 2.5–400 mg) in healthy subjects and patients undergoing myocardial reperfusion therapy. Pooled concentrations of eniporide and its metabolite from healthy subjects (n = 153; 4815 observations) and patients (n = 304; 1465 observations) were included in the pharmacokinetic analysis. Population estimates of clearance and volume of distribution of eniporide were 29.2 L/h (24.1% coefficient of variation [CV], healthy), 20.8 L/h (28.0% CV, patients) and 20.4 L (13.1% CV, healthy), 16.9 L (24.9% CV, patients), respectively. Statistical significance was achieved for the effect of age on clearance and creatinine clearance on volume of distribution of eniporide. The impact of the covariates on eniporide pharmacokinetics is minimal to warrant any dosage adjustments in patient population.