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A population pharmacokinetic‐pharmacodynamic analysis and model validation of azimilide

A population pharmacokinetic‐pharmacodynamic analysis and model validation of azimilide CLINICAL TRIALS A population pharmacoltinetic- pharmacodynamic analysis and model validation of azimilide Bac&~round: Pharmacokinetic (IX) and pharmacodynamic (I’D) models for azimilide were developed and validated with sparse blood sampling and QTc interval data obtained during three clinical trials of azim- ilide for prevention of supraventricular arrhythmia recurrence. Methods: Patients were orally administered placebo or azimilide dihydrochloride, 35, 50, 75, 100, or 125 mg/d, for 6 to 9 months. NONMEM was used for data fitting and assessment of selected patient covari- ates and concomitant medication classes for PK/PD relationships. Resdts: Results indicate that azimilide clearance (CL) was dependent on body weight (WTKG), gender, and current tobacco use, where CL (L/h) = 3.92 x (WTKG - 43)0.20s, with a 17% increase for male subjects and a 15.5% increase for current tobacco use. Volume of distribution (V) was also dependent on WTKG and total bilirubin (BIL), where V (L) = 9.88 x (WTKG - 43) + 717 x (BIL) 0 348. The PK/PD analysis indicated that the baseline QTc interval was dependent on gender, New York Heart Association Class, digoxin, and paced artificial pacemaker spike, whereas the 50% effective concentration (ECsO) was dependent on the serum potas- sium (K) level, where ECso http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Pharmacology & Therapeutics Wiley

A population pharmacokinetic‐pharmacodynamic analysis and model validation of azimilide

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References (15)

Publisher
Wiley
Copyright
© 2001 American Society for Clinical Pharmacology and Therapeutics
ISSN
0009-9236
eISSN
1532-6535
DOI
10.1016/S0009-9236(01)56650-3
Publisher site
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Abstract

CLINICAL TRIALS A population pharmacoltinetic- pharmacodynamic analysis and model validation of azimilide Bac&~round: Pharmacokinetic (IX) and pharmacodynamic (I’D) models for azimilide were developed and validated with sparse blood sampling and QTc interval data obtained during three clinical trials of azim- ilide for prevention of supraventricular arrhythmia recurrence. Methods: Patients were orally administered placebo or azimilide dihydrochloride, 35, 50, 75, 100, or 125 mg/d, for 6 to 9 months. NONMEM was used for data fitting and assessment of selected patient covari- ates and concomitant medication classes for PK/PD relationships. Resdts: Results indicate that azimilide clearance (CL) was dependent on body weight (WTKG), gender, and current tobacco use, where CL (L/h) = 3.92 x (WTKG - 43)0.20s, with a 17% increase for male subjects and a 15.5% increase for current tobacco use. Volume of distribution (V) was also dependent on WTKG and total bilirubin (BIL), where V (L) = 9.88 x (WTKG - 43) + 717 x (BIL) 0 348. The PK/PD analysis indicated that the baseline QTc interval was dependent on gender, New York Heart Association Class, digoxin, and paced artificial pacemaker spike, whereas the 50% effective concentration (ECsO) was dependent on the serum potas- sium (K) level, where ECso

Journal

Clinical Pharmacology & Therapeutics – Wiley

Published: Oct 1, 2001

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