Abstract
In congestive heart failure patients the kinetics of felodipine, a dihydropyridine calcium antagonist, show interpatient differences after acute i.v. administration that disappear after 8 weeks oral treatment with a change in kinetics in the patients with the largest clearances (CL) and the smallest volumes of distribution (V SS). Pharmacokinetic and haemodynamic data were combined to construct a haemodynamic-pharmacokinetic model. This model shows that the differences between the patients in i.v. pharmacokinetics are consistent with a difference in plasma flow distribution between liver and poorly perfused tissues. In patients in whom kinetics changed, felodipine treatment is supposed to cause a redistribution of flow from liver to peripheral tissues, accompanied by a decreased work load of the heart and a larger increase in VO2max during therapy than in the other patients, whose workload increased. This suggests a better therapeutic response in the patients whose kinetics changed. As change in kinetics is related to felodipine CL and CL to liver plasma flow, felodipine CL or even indocyanine CL might be predictive for the therapeutic effect of felodipine.
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References
Conti CR (1994) Use of calcium antagonists to treat heart failure. Clin Cardiol 17:101–102
Packer M (1990) Calcium channel blockers in chronic heart failure. The risk of “physiologically rational” therapy. Circulation 82:2254–2257
Elkayam U, Amin J, Vesquez J, et al (1990) A prospective, randomized, double blind crossover study to compare the efficacy and safety of chronic nifidepine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation 82:1954–1961
Packer M (1993) Calcium antagonists for congestive heart failure: evolving concepts in bridge building. Cardiovasc Drugs Ther 7:95
Edgar B, Reg»rdh CG, Johnsson G, Johansson L, Lundborg P, et al (1985) Felodipine kinetics in healthy man. Clin Pharmacol Ther 38:205–211
Edgar B, Collste P, Haglund K, Reg»rdh CG (1987) Pharmacokinetics and haemodynamic effects of felodipine as monotherapy in hypertensive patients. Clin Invest Med 10:388–394
Landahl S, Edgar B, Gabrielsson M (1988) Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients. A comparison with young healthy subjects. Clin Pharmacokin 14:374–383
Dunselman PHJM, Edgar B, Scaf AHJ, Kuntze CEE, Wesseling H (1989) Pharmacokinetics of felodipine after intravenous and chronic oral administration in patients with congestive heart failure. Br J Clin Pharmacol 28:45–52
Dunselman PHJM, Scaf AHJ, Wesseling H (1989) Oral pharmacokinetics of felodipine in patients with congestive heart failure: variable prediction using intravenous data. J Clin Pharmacol 29:518–523
Edgar B, Reg»rdh CG, Lundborg P, Romare S, Nyberg G, et al (1987) Pharmacokinetic and pharmacodynamic studies of felodipine in healthy subjects after various single, oral and intravenous doses. Biopharm Drug Dispos 88:235–248
Dunselman PHJM, Edgar B, Scaf AHJ, Kuntze CEE, Van Bruggen A, et al (1989) The plasma concentration-effect relationship of felodipine intravenously in patients with congestive heart failure. J Cardiovasc Pharmacol 14:438–443
Dunselman PHJM, Kuntze CEE, Van Bruggen A, Hamer JPM, Scaf AHJ, et al (1989) Efficacy of felodipine in congestive heart failure. Eur Heart J 10:354–364
Dunselman PHJM, Kuntze CEE, Van Bruggen A, Beekhuis H, Piers B, et al (1988) Value of New York Heart Association classification, radionuclide ventriculography and cardiopulmonary exercise tests for selection of patients for congestive heart failure studies. Am Heart J 116:1475–1482
Dunselman PHJM, Scaf AHJ, Kuntze CEE, Lie KI, Wesseling H (1988) Digoxin-felodipine interaction in patients with congestive heart failure. Eur J Clin Pharmacol 35:461–465
Ahnoff M, Ervik M, Johansson L (1987) Comparison of selectivity gas chromatographic methods, including column switching, for the determination of felodipine in plasma. J Chromatogr 394:419–427
Soons PA, Mulders TMT, Uchida E, Schoemaker HC, Cohen AF, Breimer DD (1993) Stereoselective pharmacokinetics of oral felodipine and nitrendepine in healthy subjects: correlation with nifedipine pharmacokinetics. Eur J Clin Pharmacol 44:163–169
Eltze M, Boer R, Sanders KH, Boss H, Ulrich WR, Flockerzi D (1990) Stereoselective inhibition of thromboxane-induced coronary vasoconstriction by 1,4-dihydropyridine calcium channel antagonists. Chirality 2:233–240
Scaf AHJ (1988) Pharmacokinetic analyses with RUGFIT; an interactive pharmacokinetic computer program. Biopharm Drug Dispos 9:415–446
Loo SCK, Riegelman S (1970) Assessment of pharmacokinetic constants from postinfusion blood curves obtained after i.v. infusion. J Pharm Sci 39:33–36
Gibaldi M, Perrier P (1982) Pharmacokinetics, 2nd edn. Marcel Dekker. New York
Leithe ME, Margorien RD, Hermiller JD, Unverferth DV, Leier CV (1984) Relationship between central hemodynamics and regional blood flow in normal subjects and in patients with congestive heart failure. Circulation 69:57–64
Binetti G, Spadoni R, Rubino I, Varani E, Ferretti RM, et al (1987) Felodipine in chronic heart failure; assessment of regional blood flow during acute test Abstract. Cardiovasc Drugs Ther 1:216
Bolt G (1985) Haemodynamic profile of felodipine, a new calcium antagonist, in conscious hypertensive rabbits. in: Vasodilators and regional blood flow. PhD Thesis, University of Leiden, pp 75–87
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Scaf, A.H.J., Wesseling, H. & Dunselman, P.H.J.M. Relationship of changes in felodipine pharmacokinetics to haemodynamics during chronic oral treatment of congestive heart failure patients. Eur J Clin Pharmacol 49, 203–210 (1995). https://doi.org/10.1007/BF00192380
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DOI: https://doi.org/10.1007/BF00192380