TY - JOUR
T1 - Determinants and significance of diltiazem plasma concentrations after acute myocardial infarction
AU - Nattel, Stanley
AU - Talajic, Mario
AU - Goldstein, Robert E.
AU - McCans, John
N1 - Funding Information:
From the Department of Medicine, Montreal Heart Institute, the Departments of Pharmacology and Therapeutics and Medicine, McGill University, the Department of Medicine, University of Montreal, the Division of Cardiology, Mortimer B. Davis Jewish General Hospital, Montreal, Quebec, Canada, and the Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland. This study was supported in part by operating grants from the Medical Research Council of Canada, the Quebec Heart Foundation, the Fonds de Recherche en Sante du Quebec and the Fonds de Recherche de l’Institut de Cardiologie de Montreal, as well as by a consortium grant from Godecke Aktiengesellschaft (Germany), Laboratorios Dr Esteve, SA (Spain), Marion Laboratories, Inc. (United States), Nordic Laboratories, Inc. (Canada), Lars Synthelabo (France), Ta-nabe Seiyaku Co., Ltd. (Japan), and Warner-Lambert International (United States). Manuscript received March 16, 1990; revised manuscript received and accepted August 8, 1990.
PY - 1990/12/15
Y1 - 1990/12/15
N2 - A total of 1,975 plasma diltiazem concentrations were obtained from 1,067 patients enrolled in a multicenter secondary intervention study of diltiazem after acute myocardial infarction. To evaluate the determinants and significance of diltiazem concentrations in this patient population, we related drug concentrations to a variety of clinical variables recorded on the case history forms. Multiple linear regression analysis showed that (1) time from the last drug dose, (2) drug dose taken, (3) patient height (an index of lean body weight), and (4) patient age were important determinants of plasma concentration. For an equivalent dose, plasma diltiazem concentrations in a 75-year-old patient were about double those of a 25-year-old patient. Total weight and drug dose prescribed did not significantly affect plasma concentrations. Whereas drug concentrations were higher (p = 0.01) among patients with left-sided heart failure, they were not altered by renal dysfunction, hepatic disease or β blockers. Diltiazem concentrations were a significant determinant of diastolic arterial pressure (p < 10-9), but neither systolic pressure nor heart rate were significantly related to diltiazem concentration. The overall incidence of adverse experiences was not related to drug concentrations, but the occurrence of second- and third-degree atrioventricular block in the coronary care unit and the need for a temporary pacemaker were substantially higher among patients with a drug concentration >150 ng/ml (7.4 and 1.9%, respectively) than among patients with lower concentrations (2.6% for atrioventricular block, 0.3% for pacemaker; p = 0.02 for each). The risk of atrioventricular block was particularly increased by high diltiazem concentrations in the face of acute inferior infarction. These results suggest that diltiazem's pharmacologic and clinical effects in a large population are concentration-related, and that the consideration of patient size, age, and left ventricular function in selecting a diltiazem dose may allow for effective drug therapy with a reduced likelihood of adverse effects.
AB - A total of 1,975 plasma diltiazem concentrations were obtained from 1,067 patients enrolled in a multicenter secondary intervention study of diltiazem after acute myocardial infarction. To evaluate the determinants and significance of diltiazem concentrations in this patient population, we related drug concentrations to a variety of clinical variables recorded on the case history forms. Multiple linear regression analysis showed that (1) time from the last drug dose, (2) drug dose taken, (3) patient height (an index of lean body weight), and (4) patient age were important determinants of plasma concentration. For an equivalent dose, plasma diltiazem concentrations in a 75-year-old patient were about double those of a 25-year-old patient. Total weight and drug dose prescribed did not significantly affect plasma concentrations. Whereas drug concentrations were higher (p = 0.01) among patients with left-sided heart failure, they were not altered by renal dysfunction, hepatic disease or β blockers. Diltiazem concentrations were a significant determinant of diastolic arterial pressure (p < 10-9), but neither systolic pressure nor heart rate were significantly related to diltiazem concentration. The overall incidence of adverse experiences was not related to drug concentrations, but the occurrence of second- and third-degree atrioventricular block in the coronary care unit and the need for a temporary pacemaker were substantially higher among patients with a drug concentration >150 ng/ml (7.4 and 1.9%, respectively) than among patients with lower concentrations (2.6% for atrioventricular block, 0.3% for pacemaker; p = 0.02 for each). The risk of atrioventricular block was particularly increased by high diltiazem concentrations in the face of acute inferior infarction. These results suggest that diltiazem's pharmacologic and clinical effects in a large population are concentration-related, and that the consideration of patient size, age, and left ventricular function in selecting a diltiazem dose may allow for effective drug therapy with a reduced likelihood of adverse effects.
UR - http://www.scopus.com/inward/record.url?scp=0025687990&partnerID=8YFLogxK
U2 - 10.1016/0002-9149(90)90527-8
DO - 10.1016/0002-9149(90)90527-8
M3 - Article
C2 - 2251986
AN - SCOPUS:0025687990
SN - 0002-9149
VL - 66
SP - 1422
EP - 1428
JO - The American Journal of Cardiology
JF - The American Journal of Cardiology
IS - 20
ER -