Effect of calcium channel blockers on theophylline disposition

  title={Effect of calcium channel blockers on theophylline disposition},
  author={Susan M. Sirmans and John Albert Pieper and Richard L. Lalonde and D Smith and Timothy H Self},
  journal={Clinical Pharmacology \& Therapeutics},
Twelve healthy subjects received a single oral dose of theophylline, 5 mg/kg alone, and after 7 days of oral verapamil, 120 mg every 8 hours, diltiazem, 90 mg every 8 hours, and nifedipine, 20 mg every 8 hours, in randomized crossover fashion. Mean theophylline oral clearance decreased 18% and 12% after verapamil and diltiazem, respectively (p < 0.05). No significant change in theophylline oral clearance was observed after nifedipine. Increases in mean theophylline half‐life were observed after… 

The effect of three different oral doses of verapamil on the disposition of theophylline

The results suggest that the inhibitory effect of verapamil on the pharmacokinetic disposition of theophylline is directly related to verAPamil dose.

The Effect of Verapamil on the Pharmacokinetic Disposition of Theophylline in Cigarette Smokers

The area under the curve (AUC0‐∞) and volume of distribution at steady‐state (Vss) for theophylline were not statistically different between the two study phases, and the relevance of a potential theophyLLine‐verapamil drug interaction remains unclear.

Clinical relevance of the interaction of theophylline with diltiazem or nifedipine.

Maximum tolerated doses of diltiazem or nifedipine do not impair the metabolism of theophylline to a clinically relevant degree and adjustment of thephylline dosage is not required after the addition or discontinuation of diltsiazem and nifingipine.

The Effect of Diltiazem on Hepatic Drug Oxidation Assessed by Antipyrine and Trimethadione

The effect of pretreatment for 3 days with diltiazem 60 mg three times a day on the pharmacokinetics of 500‐mg antipyrine and 250‐mg trimethadione was studied in six healthy male subjects, suggesting that other drugs metabolizing the same hepatic oxidative pathways as antipyrines may be influenced by diltsiazem.

The Effects of Encainide versus Diltiazem on the Oxidative Metabolic Pathways of Antipyrine

In contrast to a previously published report in rats, encainide, unlike diltiazem, does not inhibit the oxidative metabolism of antipyrine in humans.

Verapamil-Induced Inhibition of Theophylline Elimination in Healthy Humans

Increased steady-state plasma theophylline concentrations may be expected when verapamil is added to a drug regimen which includes theophyLLine.

Effects of calcium channel blockers on the pharmacokinetics of propranolol stereoisomers

Diltiazem and verapamil inhibit oxidative drug metabolism both in vivo and in vitro and decreased the unbound oral clearance of each propranolol enantiomer.

Nifedipine alters serum theophylline levels in asthmatic patients with hypertension

The effect of nifedipine on serum theophylline levels in 13 female hypertensive patients having asthma on theophyLLine therapy has been investigated and there were no changes in clinical responsiveness of either of these drugs.


Oral verapamil does not affect the disposition of oral theophylline at the dose studied, and the results showed no statistically significant difference in theophyLLine levels before and after verAPamil.

Inhibition of theophylline elimination in rabbits by verapamil.

Single intravenous dose pharmacokinetics of theophylline in 10 rabbits were investigated before and after 5 days oral administration of verapamil in daily doses of 6 mg/kg. Verapamil caused a



The interaction between i.v. theophylline and chronic oral dosing with slow release nifedipine in volunteers.

Eight healthy volunteers received a 5 min i.v. infusion of lysine theophylline both before (day 1) and during (day 5) steady state chronic oral dosing with slow release nifedipine 20 mg 12 hourly, with the greatest difference in serum theophyLLine concentrations seen at the first sampling time.

The effect of oral verapamil therapy on antipyrine clearance.

The results suggest that the inhibition of drug-metabolizing enzymes accounts for the impairment of verapamil elimination on chronic administration and half-lives measured from the concentration vs time and urinary excretion rate vs time curves were both prolonged and oral clearance was decreased.

The effect of verapamil on antipyrine pharmacokinetics and metabolism in man.

The results suggest that verapamil is capable of inhibiting oxidative metabolism, a finding which could be of clinical significance for drugs highly dependent upon pathways such as those inhibited in this study for elimination.

Diltiazem treatment impairs hepatic drug oxidation: Studies of antipyrine

Chronic oral diltiazem in therapeutic doses markedly impairs antipyrine oxidation, and may impair the clearance of other coadministered drugs that undergo hepatic oxidation.

Effect of nifedipine and theophylline in asthma

It is concluded that nifedipine has little, if any, effect on the clinical status, PEFR, or theophylline serum levels in patients with asthma who receive theophyLLine.

Pharmacokinetics and Pharmacodynamics of Nifedipine in Patients at Steady State

The steady‐state kinetic and dynamic parameter values in patients with angina pectoris in this study were similar to those found in healthy volunteers or hypertensive patients after acute nifedipine administration.

Cimetidine inhibits theophylline clearance in patients with chronic obstructive pulmonary disease: a study using stable isotope methodology during multiple oral dose administration.

Cimetidine reduced the plasma clearance of theophylline in patients with COPD to an extent similar to that reported in healthy volunteers.

Changes in antipyrine and indocyanine green kinetics during nifedipine, verapamil, and diltiazem therapy

Drug interactions with other liver‐metabolized drugs may occur during therapy with these calcium antagonists and nifedipine appears to increase liver blood flow whereas diltiazem inhibits oxidative drug metabolism.

Clinical Pharmacokinetics of Verapamil

Because of the complex pharmacokinetics associated with multiple-dose administration and the variation in individual patient responsiveness to the drug, ’standard’ dosing recommendations are difficult to determine; use of verapamil must be titrated to a clinical end-point.

Correlation between antipyrine metabolite formation and theophylline metabolism in humans after simultaneous single-dose administration and at steady state.

To nine healthy male volunteers two model substrates for oxidative drug-metabolizing enzyme activity, viz, antipyrine (A) and theophylline (T) were administered simultaneously by the p.o. route to determine whether the metabolic pathways of A and T are mediated by the same or closely related forms of the cytochrome P-450 system.