Lack of a pharmacokinetic interaction between nifedipine and the beta‐ adrenoceptor blockers metoprolol and atenolol.

Abstract

Nifedipine, metoprolol and atenolol were administered orally to young, healthy volunteers. Each drug was given alone and nifedipine was also given with both beta‐adrenoceptor blockers. Each drug was given for 3 days immediately before the study days. Plasma and urine drug concentrations were measured and the relevant pharmacokinetic parameters calculated. No pharmacokinetic interaction between nifedipine and the beta‐adrenoceptor blockers was revealed.

The interactions between nisoldipine and two beta‐adrenoceptor antagonists‐atenolol and propranolol.

“…None of these differences is statistically significant. Other studies with multiple doses of nifedipine have shown a significant effect on the disposition of propranolol (but not betaxolol) (Vinceneux et al, 1986) or alternatively no significant effects on the disposition of atenolol, propranolol and metoprolol (Gangji et al, 1984;Kendall et al, 1984), although two of these latter studies again showed higher values for the Cmax of the ,B-adrenoceptor blocker. With felodipine a significant kinetic interaction has been identified with metoprolol (Kendall et al, 1984).…”

“…Other studies with multiple doses of nifedipine have shown a significant effect on the disposition of propranolol (but not betaxolol) (Vinceneux et al, 1986) or alternatively no significant effects on the disposition of atenolol, propranolol and metoprolol (Gangji et al, 1984;Kendall et al, 1984), although two of these latter studies again showed higher values for the Cmax of the ,B-adrenoceptor blocker. With felodipine a significant kinetic interaction has been identified with metoprolol (Kendall et al, 1984). Thus, although not all studies have shown statistical significance, the weight of evidence suggests that there is a significant interaction between dihydropyridine calcium antagonists and ,B-adrenoceptor blockers (particularly, those which undergo hepatic metabolism) and it appears likely that the underlying mechanisms relate to changes in the extent of vasodilatation of the splanchnic, portal and hepatic circulations.…”

Pharmacokinetic Interactions with Calcium Channel Antagonists (Part II)

“…Kendall et al (1984) reported the results of concurrent nifedipine administration on the pharmacokinetics of metoprolol 100mg twice daily for 3 days in healthy volunteers: mean metoprolol Cmax, tmax, t'l2, CL and AUC(O-24) remained unchanged; however, plasma concentrations were not at steady-state when blood samples were drawn.…”

“…In controlled single and repeated dose trials using therapeutic dosages, nifedipine produced no significant effects on the pharmacokinetics or pharmacodynamics of metoprolol, atenolol or propranolol in healthy volunteers (Elkayam et al 1986;Gangji et al 1984;Kendall et al 1984;Rosenkranz et al 1986). However, in a double-blind, crossover study with healthy volunteers receiving propranolol 80mg every 12h, the addition of nifedipine 10mg 3 times daily increased mean total propranolol Cmax by 56% (p < 0.05) compared with propranolol alone (Vinceneux et al 1986).…”

“…During combination therapy, mean blood pressure decreased significantly and mean PR interval was reduced by 15% 2h after coadministration compared with atenol01 administration alone. Kendall et al (1984) reported the results of concomitant nifedipine lOmg every 8h administered with atenolol 100mg daily for 3 days in healthy volunteers. Mean atenolol Cmax, tmax, tv" CLR and AUC(0-24) remained unchanged.…”