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- W73993321 abstract "= 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 NON LIN 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 rela tionship 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." @default.
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- W73993321 date "1990-01-01" @default.
- W73993321 modified "2023-09-24" @default.
- W73993321 title "Pharmacokinetics and Pharmacodynamics of Intravenous Diltiazem in Dogs" @default.
- W73993321 hasPublicationYear "1990" @default.
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