Oral pharmacokinetics of felodipine in patients with congestive heart failure: variable prediction using intravenous data.
Peak and trough concentrations after 8 weeks oral therapy with felodipine, a vasodilating calcium antagonist of the dihydropyridine group, were predicted from intravenous pharmacokinetic data before therapy in 11 patients, randomly allocated to felodipine treatment 10 mg b.i.d., during a placebo controlled study in patients with congestive heart failure. Peak concentrations were well predictable, but trough levels varied between a good agreement in some patients to a large underestimation in others. Predictability was significantly correlated with half life, plasma clearance and distribution volume of the intravenous pharmacokinetic study. After 8 weeks chronic oral therapy no significant differences could be detected between the oral pharmacokinetics of predictable (n = 6) and unpredictable (n = 5) patients. This demonstrates that felodipine kinetics change during felodipine treatment. Differences in the distribution of blood flow before therapy combined with an interindividual variability in blood flow response during therapy is probably responsible for the observed impossibility to calculate trough levels, and thus oral dosage schedules, from intravenous pharmacokinetic data in patients with congestive heart failure.
Dunselman
P H
PH
Department of Cardiology, Groningen University, The Netherlands.
Scaf
A H
AH
Wesseling
H
H
D000284:Administration, Oral; D000368:Aged; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004311:Double-Blind Method; D015736:Felodipine; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009568:Nitrendipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011237:Predictive Value of Tests; D011897:Random Allocation
D002121:Calcium Channel Blockers; D009568:Nitrendipine; D015736:Felodipine