Toward optimal treatment in women: the effect of sex on metoprolol-diphenhydramine interaction

Journal of Clinical Pharmacology
Ashish SharmaB A Hamelin

Abstract

The objective of this study was to determine if sex influences the pharmacokinetics and hemodynamics of the CYP2D6 substrate metoprolol and its interaction with diphenhydramine (CYP2D6 inhibitor) in healthy young participants with high (extensive metabolizer [EM]) or low (poor metabolizer [PM]) CYP2D6 activities. A prespecified comparative analysis of data from 2 sequential clinical trials that included 16 EM and 4 PM women and 10 EM and 6 PM men was performed. The participants in the 2 trials were administered a single oral dose of 100 mg metoprolol in the presence of steady-state diphenhydramine or placebo. Serial plasma and urine samples were obtained for 48 hours, and hemodynamic data was obtained for 12 hours after metoprolol. In the placebo arm, EM and PM women had 62% and 59% higher S-metoprolol AUC(0-infinity) and 26% and 71% lower CL/F, respectively, compared to men with the same phenotype (all Ps < .05 women compared to men). These differences dissipated on body weight (WT) correction. Women (especially PMs) experienced greater negative chronotropic effects of metoprolol than men (P < .0001 women compared to men). Diphenhydramine coadministration increased S-metoprolol AUC by 84% in EM women and 45% in EM men (P < .00...Continue Reading

References

Jan 1, 1987·European Journal of Clinical Pharmacology·L J SchaafD G Perrier
Sep 1, 1987·Journal of Analytical Toxicology·G R Jones, D J Pounder
Dec 1, 1983·Clinical Pharmacology and Therapeutics·M S LennardH F Woods
Dec 29, 1999·Clinical Pharmacology and Therapeutics·A B LuzierD J Kazierad
Mar 10, 2000·Journal of Clinical Pharmacology·M E Krecic-ShepardJ B Schwartz
May 9, 2000·Clinical Pharmacology and Therapeutics·R E BentonR L Woosley
Sep 8, 2000·Clinical Pharmacology and Therapeutics·M E Krecic-ShepardJ B Schwartz
Oct 19, 2002·Clinical Pharmacology and Therapeutics·Henrike WuttkeThomas Eschenhagen
Feb 19, 2005·The Journal of Pharmacology and Experimental Therapeutics·Ashish SharmaBettina A Hamelin
Oct 8, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Wei-Yan ZhangAi-Ming Yu

❮ Previous
Next ❯

Citations

Nov 18, 2011·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Koichi Ueno, Hiromi Sato
Jul 12, 2011·Clinical Pharmacokinetics·Michel TodBruno Charpiat
May 15, 2013·Clinical Pharmacology and Therapeutics·C M BlakeP Nagele
Apr 14, 2017·CNS Drugs·Peer Tfelt-HansenJacob Tfelt-Hansen
Jul 13, 2019·Current Opinion in Pharmacology·Yasmin SchmidSimon M Mueller

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.