Steady-State Plasma Concentrations of Diltiazem and Its Metabolites in Patients and Healthy Volunteers
作者:
Yeung Pollen,
Buckley Susan,
Hung Orlando,
Pollak P.,
Barclay Katherine,
Feng Joe,
Farmer Patrick,
Klassen Gerald,
期刊:
Therapeutic Drug Monitoring
(OVID Available online 1996)
卷期:
Volume 18,
issue 1
页码: 40-45
ISSN:0163-4356
年代: 1996
出版商: OVID
关键词: Diltiazem;Diltiazem metabolites
数据来源: OVID
摘要:
SummaryDiltiazem (DTZ) is a calcium antagonist widely used in the treatment of angina and hypertension. It is extensively metabolized in humans via N-demethylation, O-demethylation, deacetylation, and oxidative deamination, yielding a host of metabolities, some of which have potent pharmacological properties. After our initial identification of O-desmethyl DTZ (Mx) and N,O-didesmethyl DTZ (MB) as major metabolites of DTZ and our subsequent of identification of their chemical synthesis, an improved high-performance liquid chromatography assay was developed to determine the plasma concentrations of DTZ and seven of its major basic metabolites, including the previously unquantitated Mx and MB. The system consisted of a C18analytical column protected by a C18cartridge guard column and a variable wavelength ultraviolet detector set at 237 nm. The mobile phase was a mixture of methanol, 0.04Mammonium acetate, and acetonitrile (38:36:26) containing 0.08% triethylamine, with final pH of the mobile phase adjusted to 7.5. The system was operated at room temperature isocratically at a flow rate of 1.2 ml/min. Using verapamil as an internal standard, DTZ and the basic metabolites in plasma were determined in young healthy volunteers (n = 21) and in patients with ischemic heart disease (n = 19) at steady state after repeated oral doses of 60 mg DTZ four times daily. Preliminary results show that steady-state plasma concentrations of DTZ and its metabolites were higher in the older patients than in young healthy subjects (p < 0.05).
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