-transparent.png){kind=logo}
In establishing a method of electrocardiographic (ECG) measurement for investigating drug-induced ECG changes, we examined the ECG effects and pharmacokinetics of terfenadine (TFN) and quinidine (QND) in rats. The time profiles of the plasma concentration and ECG parameters, such as the QT interval determined from limb lead II (QT-II) and the precordial chest lead (QT-V), heart rate and PR interval, were examined during constant intravenous infusion of TFN (5 or 15 mg/kg/h) or QND sulfate dihydrate (10 or 30 mg/kg/h). Both agents provided significant and concentration-dependent QT prolongation. The plasma concentrations (C10), where 10 ms of QT prolongation was observed, were 1.03 microM for TFN and 5.12 microM for QND, respectively. The calculated plasma unbound concentration of C10 (C10-f) was 10.3 nM for TFN and 3.82 microM for QND, which coincides with previously reported in vitro values of IC50 for potassium channels. The drug-induced QT prolongation was quantitatively reproduced in rats within the clinical concentration range. The usefulness of our methodology for the evaluation of arrhythmogenic hazards of the drugs was also demonstrated.
H Ohtani, and
E Hanada, and
K Yamamoto, and
Y Sawada, and
T Iga
April 1997,
The Journal of pharmacy and pharmacology,
H Ohtani, and
E Hanada, and
K Yamamoto, and
Y Sawada, and
T Iga
January 1993,
JAMA,
H Ohtani, and
E Hanada, and
K Yamamoto, and
Y Sawada, and
T Iga
August 2003,
British journal of clinical pharmacology,
H Ohtani, and
E Hanada, and
K Yamamoto, and
Y Sawada, and
T Iga
July 1994,
Clinical pharmacokinetics,
H Ohtani, and
E Hanada, and
K Yamamoto, and
Y Sawada, and
T Iga
January 1997,
European journal of clinical pharmacology,
H Ohtani, and
E Hanada, and
K Yamamoto, and
Y Sawada, and
T Iga
September 1996,
Clinical pharmacology and therapeutics,
H Ohtani, and
E Hanada, and
K Yamamoto, and
Y Sawada, and
T Iga
August 1993,
Journal of clinical pharmacology,
H Ohtani, and
E Hanada, and
K Yamamoto, and
Y Sawada, and
T Iga
March 1993,
Clinical pharmacology and therapeutics,
H Ohtani, and
E Hanada, and
K Yamamoto, and
Y Sawada, and
T Iga
January 2001,
Xenobiotica; the fate of foreign compounds in biological systems,
H Ohtani, and
E Hanada, and
K Yamamoto, and
Y Sawada, and
T Iga
November 2017,
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences,
