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Pharmacokinetics and Pharmacodynamics of Intravenous Diltiazem in Dogs
마취견에서 Ditiazem의 약동학 및 약력학 연구

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Authors
Han, Sun-Hwa; Chung, Myung-Hee; Cha, In-Jun
Issue Date
1990-03
Publisher
Seoul National University College of Medicine
Citation
Seoul J Med 1990;31(1):1-10
Keywords
DiltiazemPharmacokineticsPharmacakinetic-Pharmacadynamic analysisDog
Abstract
The phannacokinetic and cardiovascular effects of dilitiazem were studied in
six adult dogs after intravenous infusion of diltiazem HCI over a period of 10 minutes.
Plasma drug concentrations, P-R intervals on EKG, blood pressure and heart rate changes
were serially measured upto six hours after drug administration. To analyze the effect site
concentration-effect relationships of diltiazem, plasma drug concentrations and response data
were fitted to a three-compartment phannacokinetic/pharmacodynamic model with NONLIN
program. Plasma diltiazem levels peaked at 743.1 ± 224.6 ng/ml in about 1 mg/kg
dose in four dogs, 1151.5 ng/ml in 1.43 mg/kg dose and 1177.4 ng/ml in 1.85 mg/kg
dose and thereafter decreased triexponentially. The terminal half-life estimated was 2.0 ±
0.5 hours, and the volume of distribution at steady-state(Vdss) and the total body clearance
were 4.42 ± 0.87 L/kg and 25.5 ± 6.6 L/hr, respectively. After intravenous diltiazem, the
P-R interval increased upto 27.79 ± 12.48'1'0 in about 1.0 mg/kg, and 34.25% in 1.43 mg/
kg and 45.42% in 1.85 mg/kg dose. Diastolic blood pressure decreased upto 16.75 ±
8.26% in about 1 mg/kg, 19.69'Yo in 1.43 mg/kg and 30.45°;;, in 1.85 mg/kg dose.
Counterclockwise hysteresis curve was found in the P-R interval prolongation vs. the plasma
dilitiazem concentration curve. The P- R interval prolongation - effect site concentration relationship
was best explained by the linear model except for one dog, in which Emax model
was best applied. The estimated equilibration rate constant(keo) between plasma and effect
site was 0.46 ± 0.33 min-I, and slope for the linear model was 0.063 ± 0.002. Emax and
ECso were estimated as 99 msec and 667 ng/ml in one dog. The blood pressure-effect site
concentration relationship was best fitted by a linear model in all six dogs, and the estimated
keo and slope of the relationship were >1 min I and 0.069 ± 0.042, respectively.
ISSN
0582-6802
Language
English
URI
http://hdl.handle.net/10371/7290
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)The Seoul Journal of MedicineThe Seoul Journal of Medicine Vol. 31 No.1 (1990)
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