The purpose of this study was to test whether carvedilol improves hepatic function and to determine the changes in carvedilol pharmacokinetics in the setting of liver fibrosis. Various tests were completed in rats to measure hepatic blood flow, as well as synthetic and metabolic capacity.
Three of the four main components of PK were described in the introduction of the paper. Oral absorption of carvedilol is both rapid and complete. Extensive metabolism occurs in the liver. Elimination of the drug occurs via several mechanisms, which are explained in greater detail later in this paper. Although distribution of the drug is not specifically mentioned in the introduction, the volume of distribution (Vd) in rats is listed for the four test groups, …show more content…
time graphs. The area under the concentration-time curve from 0 to infinity (AUC0∞) was estimated using the trapezoidal rule and adding C/k_el , where C is the last concentration used in the trapezoidal calculation, and kel is the elimination rate constant. The increase in AUC for carvedilol was related to the decrease in clearance for rats given CCl4 in all three treatment groups compared to control. The carvedilol plasma concentration was higher in rats with liver fibrosis. According to the concentration vs. time profiles, the tmax seems to be around 2 hours. However, the true tmax may be slightly lower or higher, since blood samples were only taken at 10 and 30 minutes and at 1, 2, 4, and 24 hours after drugs were administered (or not administered, as for the control group). Cmax was higher (263.50 ng/mL vs. 225.20 ng/mL) in rats after induction of liver fibrosis. This is a sensible result because the carvedilol was not metabolized or eliminated as quickly due to the decreased liver function. It was also reasonable that the Cmax was lower (253.3 ng/mL vs. 259.7 ng/mL) in rats treated with carvedilol after liver fibrosis was
Three of the four main components of PK were described in the introduction of the paper. Oral absorption of carvedilol is both rapid and complete. Extensive metabolism occurs in the liver. Elimination of the drug occurs via several mechanisms, which are explained in greater detail later in this paper. Although distribution of the drug is not specifically mentioned in the introduction, the volume of distribution (Vd) in rats is listed for the four test groups, …show more content…
time graphs. The area under the concentration-time curve from 0 to infinity (AUC0∞) was estimated using the trapezoidal rule and adding C/k_el , where C is the last concentration used in the trapezoidal calculation, and kel is the elimination rate constant. The increase in AUC for carvedilol was related to the decrease in clearance for rats given CCl4 in all three treatment groups compared to control. The carvedilol plasma concentration was higher in rats with liver fibrosis. According to the concentration vs. time profiles, the tmax seems to be around 2 hours. However, the true tmax may be slightly lower or higher, since blood samples were only taken at 10 and 30 minutes and at 1, 2, 4, and 24 hours after drugs were administered (or not administered, as for the control group). Cmax was higher (263.50 ng/mL vs. 225.20 ng/mL) in rats after induction of liver fibrosis. This is a sensible result because the carvedilol was not metabolized or eliminated as quickly due to the decreased liver function. It was also reasonable that the Cmax was lower (253.3 ng/mL vs. 259.7 ng/mL) in rats treated with carvedilol after liver fibrosis was