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

  title={The effect of three different oral doses of verapamil on the disposition of theophylline},
  author={Kathleen A. Stringer and Jane Mallet and M. Clarke and Jo Ann Lindenfeld},
  journal={European Journal of Clinical Pharmacology},
SummaryResults of previous studies suggest that the theophylline-verapamil drug interaction may be dependent on verapamil dose. Therefore, in a randomized four-way cross over study, 12 healthy males received theophylline, as a single intravenous dose of aminophylline, alone (phase I) and after a four day regimen of oral verapamil 40 mg (phase II), 80 mg (phase III), and 120 mg (phase IV) every 8 h. Serial blood samples were collected over a 24 hour period for determination of serum theophylline… 

Drug-Drug Interactions: Influence of verapamil on the pharmacokinetics of sitagliptin in rats and Ex vivo models

Results revealed that verapamil enhanced the bioavailability of sitagliptin probably by inhibiting its absorption via P-gp and/or the CYP3A4mediated biotransformation in rats.

Pharmacokinetic interaction study between flavanones (hesperetin, naringenin) and rasagiline mesylate in wistar rats

Hesperetin and naringenin co-administration significantly enhanced the area under the curve (AUC), maximum plasma concentration (Cmax) and elimination half life (t1/2) of rasagiline with a concomitant reduction in clearance (CL/F) in both SDS and MDS.

Drug Interactions for Low-Dose Inhaled Nemiralisib: A Case Study Integrating Modeling, In Vitro, and Clinical Investigations

Assessment of victim and perpetrator risks of drug transporters and cytochrome P450 enzymes is featured, utilizing empirical and mechanistic approaches combined with clinical data and physiologically based pharmacokinetic modeling approaches to facilitate bespoke risk assessment in target patient populations.

Influence of nifedipine, nitrendipine and verapamil at low concentration on antipyrine metabolism examined by extracorporeal rat liver perfusion.

The present experiment suggests that low concentrations of CCI can exert hepatoprotective effect, however, confirmation of this conclusion requires further studies using other experimental methods.

A Physiologically Based Pharmacokinetic Model to Predict Disposition of CYP2D6 and CYP1A2 Metabolized Drugs in Pregnant Women

The PBPK model can predict the disposition of CYP1A2, 2D6, and 3A drugs during pregnancy and suggests that the magnitude of hepatic CYP2D6 induction during T3 ranges from 100 to 200%.

Pharmacokinetic drug-drug interactions in the intensive care unit - single-centre experience and literature review.

DDIs as well as their side-effects are challenging regarding their precise evaluation, especially due to the need for multidrug treatment in critically ill patients, so concentration-controlled therapy should be recommended, especially for treatment with vancomycin, digoxin and valproate.

Vrednotenje procesa terapevtskega spremljanja serumskih koncentracij teofilina

Theophylline TDM service should be optimized and pharmacokinetic interpretation of theophyllines serum levels should be integrated into clinical practice.

Volume of Distribution is Unaffected by Metabolic Drug–Drug Interactions

The results support the widely held founding tenant of pharmacokinetics that clearance and V ss are independent parameters and can be helpful in discriminating changes in clearance from changes in bioavailability when only oral dosing data are available.

A Re-evaluation and Validation of Ontogeny Functions for Cytochrome P450 1A2 and 3A4 Based on In Vivo Data

Background and ObjectivesCurrent cytochrome P450 (CYP) 1A2 and 3A4 ontogeny profiles, which are derived mainly from in vitro studies and incorporated in paediatric physiologically based

A Mechanistic Approach for the Scaling of Clearance in Children

Paediatric clinical trial development could greatly benefit from clearance scaling, particularly in guiding dosing regimens, since the proportion of clearance via different elimination pathways is age-dependent and information could be gained on the developmental extent of drug-drug interactions.



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.

Effect of calcium channel blockers on theophylline disposition

The modest reduction in theophylline clearance observed after verapamil and diltiazem is not likely to produce clinically significant increases in thephylline concentrations in most patients.

Substrate-selective inhibition by verapamil and diltiazem: differential disposition of antipyrine and theophylline in humans.

Antipyrine and theophylline disposition was studied in healthy volunteer subjects in the control state while the subjects were taking verapamil orally four times daily or diltiazem orally three times daily, resulting in prolonged antipyrine half-life with no change in distribution volume.

Selective inhibitory effects of nifedipine and verapamil on oxidative metabolism: effects on theophylline.

Verapamil and nifedipine at usual clinical doses are unlikely to cause clinically significant changes in theophylline disposition.

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.

Inhibition of hepatic microsomal drug metabolism by the calcium channel blockers diltiazem and verapamil.

  • K. Renton
  • Biology, Chemistry
    Biochemical pharmacology
  • 1985

Calcium Antagonists in the Management of Asthma: Breakthrough or Ballyhoo?

Data has been generated on the effects of verapamil, diltiazem, nifedipine, and several investigational agents on experimentally induced asthma, indicating that none of these agents significantly affects resting bronchomotor tone, and their efficacy in preventing bronchospasm is a function of the drug, dose, route of administration and method of bronchoprovocation.

Calcium-channel blocking agents for gastrointestinal disorders.

  • D. O. Castell
  • Medicine, Biology
    The American journal of cardiology
  • 1985

Calcium and stimulus-secretion coupling in gastric fundic mucosa. Effect of inhibition of calcium transport by verapamil on gastric acid secretion in the isolated guinea pig fundic mucosa and in healthy subjects.

It is concluded that one of the mechanisms by which extracellular calcium concentration influences acid secretion is by transmembrane influx of Ca2+ during stimulation.

Noncompartmental Analysis Based on Statistical Moment Theory