Evaluation of the antianginal effect of nifedipine: influence of formulation dependent pharmacokinetics.
Nifedipine capsules t.d.s. and an extended release formulation of nifedipine, nifedipine-ER tablets, given once daily in corresponding daily doses, have been compared with placebo in a double-blind, three-way cross-over study in 24 patients with stable angina pectoris. The objective was to study the influence on the antianginal effect of the different pharmacokinetics of several preparations of nifedipine. All patients received concomitant treatment with beta-adrenoceptor blockers. Antianginal efficacy was assessed by a dynamic exercise test at the end of the dosage intervals, i.e. 8 and 24 h after nifedipine capsules and nifedipine-ER, respectively, as well as 6 h after dosing. Six h after dosing the time of onset of chest pain and total exercise time were longer and total work was significantly higher during both nifedipine-ER (plasma concentration 260 nmol/l) and placebo treatment than after nifedipine capsules (plasma concentration 78 nmol/l). Time to 1 mm ST depression was longer during nifedipine-ER than during nifedipine capsule treatment. No significant difference was seen between nifedipine-ER and placebo. At the end of the dosage interval (24 and 8 h after nifedipine-ER and nifedipine capsules, respectively), no significant difference was found between nifedipine-ER (plasma concentration 75 nmol/l) and the other two treatments. However, placebo was superior to nifedipine capsules (plasma concentration 58 nmol/l) both in the time to onset of chest pain and total exercise time. The lack of effect at the end of the dosage interval was probably due to the subtherapeutic plasma nifedipine level.(ABSTRACT TRUNCATED AT 250 WORDS)
Karlson
B W
BW
Department of Medicine I, Sahlgrenska Hospital, Göteborg, Sweden.
Emanuelsson
H
H
Herlitz
J
J
Nilsson
J E
JE
Olsson
G
G
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D005080:Exercise Test; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013607:Tablets
D003692:Delayed-Action Preparations; D013607:Tablets; D009543:Nifedipine