Pharmacokinetic interaction between metoprolol and SP-8203 in rats: competitive inhibition for the metabolism of metoprolol by SP-8203 via hepatic CYP2D subfamily.
Summary of "Pharmacokinetic interaction between metoprolol and SP-8203 in rats: competitive inhibition for the metabolism of metoprolol by SP-8203 via hepatic CYP2D subfamily."
The occurrence of cerebral ischemia is prevalent in patients with hypertension and the combination drug therapy is needed. Thus, the pharmacokinetic interaction between metoprolol (anti-hypertension drug) and SP-8203 (a new drug candidate for cerebral ischemia) with respect to the metabolism via CYP isozymes was evaluated. Metoprolol and SP-8203 were administered intravenously or orally to rats. Concentrations (I) of each drug in the liver and intestine in in vivo studies, the disappearance and apparent K(i) of each drug in in vitro microsomes and [I]/K(i) ratios for each drug were determined. In addition, the disappearance of each drug via CYPs in rat and human microsomes were measured. The AUC and CL(NR) of intravenously administered metoprolol with SP-8203 were significantly greater and slower, respectively, than without SP-8203. However, pharmacokinetic parameters of oral metoprolol and intravenous/oral SP-8203 were not altered. The hepatic metabolism of metoprolol via CYP2D was inhibited by SP-8203 in a competitive manner. However, the intestinal metabolism of metoprolol was not influenced by SP-8203. SP-8203 was not metabolized via CYP isozymes in rats and then co-administration of metoprolol did not affect the metabolism of SP-8203.
College of Pharmacy, Dongguk University-Seoul , Seoul , South Korea.
This article was published in the following journal.
Name: Xenobiotica; the fate of foreign compounds in biological systems
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22568632
- DOI: http://dx.doi.org/10.3109/00498254.2012.663117
Medical and Biotech [MESH] Definitions
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
An outbred strain of rats developed in 1915 by crossing several Wistar Institute white females with a wild gray male. Inbred strains have been derived from this original outbred strain, including Long-Evans cinnamon rats (RATS, INBRED LEC) and Otsuka-Long-Evans-Tokushima Fatty rats (RATS, INBRED OLETF), which are models for Wilson's disease and non-insulin dependent diabetes mellitus, respectively.
Mutant strains of rats that produce little or no hair. Several different homozygous recessive mutations can cause hairlessness in rats including rnu/rnu (Rowett nude), fz/fz (fuzzy), shn/shn (shorn), and nznu/nznu (New Zealand nude). Note that while NUDE RATS are often hairless, they are most characteristically athymic.
A trypanosome found in the blood of adult rats and transmitted by the rat flea. It is generally non-pathogenic in adult rats but can cause lethal infection in suckling rats.
Rats, Inbred Dahl
Inbred rats derived from Sprague-Dawley rats and used for the study of salt-dependent hypertension. Salt-sensitive and salt-resistant strains have been selectively bred to show the opposite genetically determined blood pressure responses to excess sodium chloride ingestion.
Objective: To develop a pharmacokinetic model able to describe the nonlinear pharmacokinetics of paroxetine (PRX) and to predict the drug-drug interaction between PRX and metoprolol under various dosa...
Flavonoid extracts are widely used for preventing and treating ischemic heart disease. However, because many flavonoid extracts have been verified to inhibit CYP2D6 the main metabolic enzyme for the m...
Clinical studies revealed that some fluoroquinolones may cause severe adverse effects when co-administered with substrates of CYP1A2. Our previous study showed antofloxacin (ATFX) mechanism-basely inh...
To examine the effects of metoprolol on expression of myocardial inflammatory cytokines and myocardial function in rats following coronary microembolization (CME).
We have previously shown that metoprolol improves function in the diabetic heart, associated with inhibition of fatty acid oxidation and a shift towards protein kinase B signaling. The aim of this stu...
The primary aim was to evaluate the relief of chest pain during the first 30 minutes among patients who received metoprolol alone as compared with metoprolol plus morphine
This is a randomised, open-label; parallel group, multicentric study comparing the efficacy and safety of fixed-dose-combinations of Metoprolol XL plus Amlodipine with individual component...
We will compare three study groups receiving metoprolol, esmolol, or placebo. Level of anesthesia will be titrated to achieve the same range of BIS value in all groups. Our hypothesis is t...
The purpose of this study is to compare the tolerability of nebivolol to metoprolol ER in a populatoin of patients with mild to moderate hypertension also receiving hydrochlorothiazide (HC...
A randomized, open-label, six-sequence, three-period, three-treatment, multiple dosing clinical trial to investigate the pharmacokinetic drug interaction between Pregabalin and Thioctic ac...