Factors determining the response to calcium antagonists in hypertension.
Pharmacokinetic and pharmacodynamic variability account for the large interindividual differences in the antihypertensive response to treatment with a calcium antagonist. Using an integrated kinetic-dynamic model, the acute and chronic (4-6 weeks) responses to nifedipine (n = 14) and verapamil (n = 14) were characterized for individual hypertensive patients in terms of fall in blood pressure per unit drug concentration. The responsiveness to nifedipine, as the mean of the group, was -0.48 mm Hg/ng/ml following the first dose and -0.49 mm Hg/ng/ml after chronic dosing. The corresponding values for verapamil were -0.13 and -0.12 mm Hg/ng/ml, respectively. For nifedipine and verapamil, the responsiveness to the first dose was significantly correlated both with the height of the pretreatment blood pressure (p less than 0.001) and the responsiveness after 4-6 weeks of treatment (p less than 0.001). Parameters derived from an individual approach to concentration-effect analysis are useful for evaluating the determinants of response to calcium antagonists and form a potential basis for optimizing drug therapy in individual patients.
Donnelly
R
R
University Department of Materia Medica, Stobhill Hospital, Glasgow, Scotland.
Reid
J L
JL
Meredith
P A
PA
Ahmed
J H
JH
Elliott
H L
HL
D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000493:pharmacokinetics / Q000627:therapeutic use; D013564:Sympathetic Nervous System / Q000187:drug effects; D014700:Verapamil / Q000493:pharmacokinetics / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D014700:Verapamil; D009543:Nifedipine