Nifedipine infusion in acute myocardial infarction: experience in twelve patients.
Studies of nifedipine have not shown that it reduces myocardial infarct size in humans. These studies did not consider the pharmacokinetics and dynamics of nifedipine. Oral doses of nifedipine cause high plasma concentrations and possibly harmful hemodynamic changes. Intravenous nifedipine infusion can rapidly achieve and maintain a steady concentration without repeated hemodynamic upsets. We studied 24-h intravenous nifedipine infusion in 12 patients with acute myocardial infarct, starting within 6 (mean 4.0 +/- 0.7) h of onset of pain, to determine its safety, pharmacokinetics, and dynamics. An intravenous nifedipine bolus of 15 micrograms/kg was followed by an infusion of 0.9 mg/h for 24 h. After the bolus, pulse rate rose 12.5 +/- 8.0 p less than 0.01) and blood pressure fell (systolic by 20 +/- 34, p less than 0.05, and diastolic by 7.5 +/- 15.6, p less than 0.05). There were similar but lesser changes during the infusion. Myocardial oxygen requirements, as measured by the rate-pressure product, did not increase. The mean nifedipine concentration at steady state was 17.2 +/- 4.2 ng/ml and mean elimination T 1/2 3.57 +/- 2.70 h. Nifedipine was discontinued in 3 patients because of hypotension (SBP less than 90), rapid atrial fibrillation, and complete heart block in one patient each. Seven patients developed thrombophlebitis. Large studies of this preparation examining infarct size limitation and mortality are feasible, although in view of the problems of thrombophlebitis in peripheral veins, shorter infusion times or infusion via central lines would be more acceptable.
Department of Pharmacology and Therapeutics, University of Leicester, United Kingdom.
T J
TJ
Walley
A M
AM
Heagerty
K L
KL
Woods
R F
RF
Bing
J E
JE
Pohl
D B
DB
Barnett
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy*; D009543:Nifedipine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D010865:Pilot Projects; D013924:Thrombophlebitis / Q000209:etiology
D009543:Nifedipine