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Felodipine kinetics in healthy men
Author(s) -
Edgar Boo,
Regårdh C G,
Johnsson G,
Johansson L,
Lundborg P,
Löfberg I,
Rönn O
Publication year - 1985
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1985.160
Subject(s) - felodipine , volume of distribution , pharmacokinetics , chemistry , dosing , absorption (acoustics) , distribution (mathematics) , oral administration , crossover study , volume (thermodynamics) , pharmacology , anesthesia , medicine , endocrinology , materials science , placebo , mathematics , mathematical analysis , alternative medicine , composite material , pathology , blood pressure , quantum mechanics , physics
In a randomized, crossover study, the absorption, distribution, and elimination of intravenous and oral felodipine were investigated in eight healthy men 22 to 31 years old. Felodipine was given as a 2.5 mg iv infusion over 30 minutes and as a 27.5 mg oral solution. Both doses were labeled with 25 µCi 14 C‐felodipine. Given as an oral solution, felodipine is rapidly (mean time to peak concentration 64 minutes; range 30 to 90 minutes) and completely absorbed. Presystemic elimination reduced the availability to 16% (range 10% to 25%). Felodipine kinetics can be described by a multicompartmental model with three distinct phases. The t ½ for the initial phase was 6.4 minutes (range 1.7 to 10.4 minutes) and felodipine was distributed to a volume of 0.6 L/kg (range 0.4 to 0.9 L/kg), which approximately corresponds to the total body water. The second distribution phase reached pseudoequilibrium with a t ½ of 1.6 hours (range 1.3 to 2.2 hours). The volume of distribution at the end of this phase was 9.7 L/kg (range 6.0 to 18.2 L/kg). The terminal phase had t ½ of 10.2 hours (range 6.7 to 20.7 hours). The contribution of the three phases to the AUC was 15%, 40%, and 45% in the order of increased t ½ . Total body clearance of felodipine was 1.2 L/min (range 0.9 to 1.6 L/min). Within 72 hours after drug dosing, 62% to 81% of the felodipine doses were excreted in the urine and feces as metabolites. The rate of excretion by the kidneys had a biphasic pattern, with t ½ values of 4 and 18 hours. Approximately 10% of the doses was excreted in the feces. Clinical Pharmacology and Therapeutics (1985) 38, 205–211; doi: 10.1038/clpt.1985.160