title: Population pharmacokinetics of eniporide and its metabolite in healthy subjects and patients with acute myocardial infarction.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, PO Box 100494, JHMHC, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Venkatesh Atul
authors.initials: VA
authors.lastname: Bhattaram
authors.forename: Nelamangala V
authors.initials: NV
authors.lastname: Nagaraja
authors.forename: Tanja
authors.initials: T
authors.lastname: Peters
authors.forename: Thomas
authors.initials: T
authors.lastname: Machnig
authors.forename: Sonja
authors.initials: S
authors.lastname: Kroesser
authors.forename: Andreas
authors.initials: A
authors.lastname: Kovar
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D012189:Retrospective Studies; D017923:Sodium-Hydrogen Exchangers / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism; D013450:Sulfones / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*
chemical_list: C506755:EMD 112843; D006146:Guanidines; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C118397:eniporide