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Pharmacokinetic and pharmacodynamic studies of felodipine in healthy subjects after various single, oral and intravenous doses
Author(s) -
Edgar Boo,
Regårdh Carl G.,
Lundborg Per,
Romare SÖRen,
Nyberg Gunnar,
Rönn Ola
Publication year - 1987
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510080305
Subject(s) - felodipine , pharmacokinetics , blood pressure , pharmacodynamics , pharmacology , antagonist , oral administration , heart rate , medicine , hemodynamics , anesthesia , receptor
The objective of this single‐dose study was to evaluate the pharmacokinetics and haemodynamic changes in healthy male subjects following the administration of three oral (5, 15, and 40 mg) and two intravenous (1 and 3 mg) doses of felodipine, a new calcium antagonist with a selective effect on the peripheral resistance vessels. Felodipine was rapidly absorbed within 1 h when administered as an oral solution, but underwent extensive presystemic elimination. The systemic availability varied between 10 and 23 per cent. The disposition was adequately described by a two‐compartment model: the disposition was essentially dose‐independent up to 40 mg orally and 3 mg intravenously. Felodipine produced significant dose‐dependent reduction of diastolic blood pressure and a significant reflexogenic increase in heart rate, without having any major effect on systolic blood pressure. These changes indicate that felodipine acts predominantly as an arteriodilator. The decrease in diastolic blood pressure and increase in heart rate were closely correlated with the plasma concentrations of unchanged felodipine, being maximal at 0.5 h and lasting for at least 4 h after the highest dose.