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Lecture 4 Notes (Drug Metabolism and Excretion Part 2)
Pharmacology And Toxicology
Royal Holloway, University of London
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Pharmacology and Toxicology
Lecture 4 Notes: Drug Metabolism and Excretion Part 2
Age significantly affects the half-life of a drug because the ability of the kidneys to drugs falls with age. Therefore, the plasma half-life of a drug increases linearly with age. Additionally, a patients renal function greatly affects how much drug can be administered. It is possible to estimate the degree of renal impairment by measuring creatinine clearance, from which the dose of a drug can be adjusted accordingly. Depending on the rate of renal clearance of creatinine (i. GFR), the dose and frequency of gentamicin must be adjusted accordingly. Rate of administration decreases as the GFR falls dramatically. This is because it is difficult for the kidneys to clear this drug efficiently as the half-life of the drug increases with increased kidney impairment. Therefore, kidney disease and its severity effects how much of a drug is given to a patient.
For example, if a drug is given at a low dose, it will be below the minimal effective concentration so the desired effect of the drug will not be seen. However, if the patient has a very low clearance rate, even a normal dosage can be fatal (above the minimum toxic concentration of a drug). For example, a drug at a dose of 3g was taken orally by an 80kg volunteer. Blood samples were withdrawn at regular time intervals and the plasma concentration of the un-metabolised drug was determined using an HPLC technique.
Bioavailability of this preparation is 67%. To determine the biological half-life, elimination rate constant, volume of distribution and plasma clearance of this drug, the time after administration and the natural log of the plasma concentration of the drug are plotted on a graph. To estimate the half-life of this drug from the graph, we take the point at which the concentration of the drug peaks and then calculate how long it takes for it to fall to half of this original value. In this example, the concentration drops from 13 μg (2 ln on graph) to 6 μg/ml (1 on graph). This takes 2 hours. From this we can rearrange the formula for t0 to calculate the kel. For example, kel = 0.693/2. Therefore, the elimination rate constant is 0 hr-1. To calculate the VD, we can extrapolate a straight line from the graph to the y-axis and convert from the natural log to calculate the C 0 P (50μg/ml or 0). The initial dose (Q) is 3g and bioavailability is 67%. Therefore, only 3 x 0 is reaching the bloodstream (2 or 2010mg). Thus, we use the equation to calculate VD (Q/C 0 P). Thus, 2010/0 is 40200 ml or 40 litres. To calculate CLT, multiply kel by VD (0 hr-1 x 40 L). Thus, CLT is 11 L/hr.
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Lecture 4 Notes (Drug Metabolism and Excretion Part 2)
Module: Pharmacology And Toxicology
University: Royal Holloway, University of London
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Students also viewed
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- Lecture 2 Notes (Measurements of Ligand Affinity Part 2)
- Lecture 2 Notes (Measurements of Ligand Affinity)
- Lecture 1 Notes (Agonists, Antagonists and Potency Part 3)