Plasma concentration-effect relationships of intravenous and extended-release oral felodipine in hypertensive patients.
Felodipine, a dihydropyridine calcium antagonist, was given double-blind in a crossover design comparing once-daily doses of 20 mg felodipine extended-release (ER) tablets with placebo in 12 hypertensive patients. A 2-h intravenous infusion was given after a placebo washout. After oral felodipine, blood pressure (BP) was significantly lower than after placebo, both after the first dose and after 2 weeks of treatment. Supine BP 24 h after the first dose of placebo and felodipine was 159/97 and 153/92 mm Hg (p less than 0.01/0.05), respectively. Corresponding BPs at 2 weeks were 158/99 and 144/89 mm Hg (p less than 0.01/0.01). Approximately 75% of the maximal and 60% of the trough effect at steady state were obtained already after the first dose. The plasma concentration (CpF) vs. time curve after felodipine ER was relatively flat. After oral felodipine, a linear correlation was found between BP reduction and logarithmic CpF. After intravenous administration, CpF correlated well with a hyperbolic function. These data indicate that there is an almost linear relation between BP reduction and log CpF in the range from 2-20 nmol/L, and that little additional effect is to be expected above approximately 20 nmol/L. No hysteresis was found for the relationship between CpF and BP reduction. The absolute bioavailability of felodipine ER was 22%.
Blychert
E
E
Department of Clinical Pharmacology, Sahlgrenska Hospital, Göteborg, Sweden.
Hedner
T
T
Dahlöf
C
C
Elmfeldt
D
D
D000328:Adult; D000368:Aged; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D015736:Felodipine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged
D003692:Delayed-Action Preparations; D015736:Felodipine