Steady-state pharmacokinetics of high-dose diltiazem hydrochloride (Cardizem CD) administered once daily in healthy volunteers

American Journal of Therapeutics
D K Robbins-WeilertS J Weir

Abstract

The once-daily formulation of diltiazem hydrochloride (Cardizem CD) is marketed for the treatment of essential hypertension and stable angina pectoris. The steady-state pharmacokinetics of once-daily diltiazem and its metabolites, desacetyldiltiazem (DAD) and N-desmethyldiltiazem (MA), were examined in two groups of eight healthy subjects each. The first group (group A) received 240, 480, and 720 mg diltiazem once daily for 7 days in a single-blind, stair-step, dose-escalation design. The second group (group B) received 180, 360, and 720 mg diltiazem in a similar manner. At each dose level, serial blood samples were collected for up to 24 hours after the last (seventh) dose. Plasma samples were analyzed for diltiazem and the metabolites by high-performance liquid chromatography. The disposition of diltiazem, DAD, and MA was nonlinear over the 240- to 720-mg (group A) and 180- to 720-mg (group B) diltiazem dose ranges studied. In group A, mean diltiazem area under the plasma concentration-time curve (AUC) at the 240-mg dose level was 2410 h.ng/mL compared with 10,167 h.ng/mL at the 720-mg dose level. In group B, mean diltiazem AUC at the 180-mg dose level was 1092 h.ng/mL compared with 8398 h.ng/mL at the 720-mg dose level. The ...Continue Reading

Citations

Jun 13, 2017·Pharmaceutical Development and Technology·Laila H EmaraNesrin F Taha

❮ 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.