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Phoenix WinNonLin Assignment Due Today Access Phoenix remotely.
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Phoenix WinNonLin Assignment Due 8/31/15 Import Simulated Data in Phoenix, Plot it in Phoenix and put it into a MS Word document.
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LOGARITHM REVIEW Lecture #4
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History of Logs John Napier (1614) and Joost Burgi (1620) Why? Simplify astronomical calculations. Multiplication was a simplification of addition – 3 x 5 = 5+5+5 Powers are a simplification of multiplication – 5 3 = 5 x 5 x 5 Division is the opposite of Multiplication Logs are opposite to Powers
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What do logs do? Allows you to see the relationship between things? Linear Scale Log Scale Makes curves straight.
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Logs log base answer = power base power = answer Powers
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Powers to Logs Powers VersionLog Version 10 2 =100log 10 100=2 3 2 =9log 3 9=2 e 3 =20.085log e 20.085=3 e -kt = Clog e C = -kt What is e? =~2.718 * derived from an infinite series.
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Properties of Logs: Positive Logs Implicit assumption log = log 10 ln = log e Log 1 = 0 Log 10 = 1 Log 100 = 2
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Property of Logs: Negative Logs Log 0.1 = -1 Log 0.01 = -2 Log 0.001 = -3
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Properties of Logs
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KINETIC CONCEPTS Lecture #4
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Things you will learn Fractional elimination rate constant (k) Half-time (t 1/2 ) Mean residence time (MRT) Extraction ratio (E) Amount of Drug (A) Volume distribution (V) Clearance (CL)
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Linear/Cartesian PlotSemilogarithmic plot Fractional Elimination Rate (k) = - slope Linear vs. Log
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Linear/Cartesian Plot Fractional Elimination rate (k) = - slope Semilogarithmic Plot Which one has the higher rate? Linear vs. Log
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Half-Life (t1/2) Time in which the [drug] is half the initial [drug]
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Mean Residence Time (MRT) MRT = Average time that a molecule stays in the body
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Concentration mg L mg/L C = [Drug] V = Volume Distribution
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[Drug] Reservoir
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[Drug] Reservoir Blood Flow (Q)
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[Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted
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[Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted [Drug] Extracted = C-C out Initial [Drug] = C
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Extraction Ratio
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[Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted How fast are drugs presented to the extractor (mg/hr)?
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[Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted How fast are drugs eliminated by the extractor (mg/hr)?
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[Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted What is the volume of blood with drug extracted per hour?
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[Drug] Reservoir Blood Flow (Q) Extractor C C out [Drug] Extracted Clearance
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Amount of Drug (A) in the Blood C = [Drug] (mg/L) V = Volume Distribution (L) A (mg) = C (mg/L) * V (L) Example C=100 mg/L V=5L, which is the average volume of blood A=C*V=500 mg of drug in the blood
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Volume Distribution (V) C={Drug] Blood Average Volume of Blood = 5L 5L Dose = 500 mg C(0) = 100 mg/L A=500 mg What is the V? 500 mg 5L A = Amount of Drug in the Blood (mg)
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Volume Distribution (V) C={Drug] Blood Average Volume of Blood = 5L 5L Dose = 500 mg C(0) = 50 mg/L A=250 mg What is the V? 250 mg Brain 250 mg 10 L A = Amount of Drug in the Blood (mg)
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Volume Distribution (V) C={Drug] Blood Average Volume of Blood = 5L 5L Dose = 500 mg C(0) = 2 mg/L A=10 mg What is the V? 10 mg Brain 490 mg 250 L A = Amount of Drug in the Blood (mg)
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What does Volume Distribution (V) Tell Us? If V=~5L, tells us that the drug is primarily in the blood. If V>5L, that is typical. If V>>5L, tells us that the drug is distributed away from the blood. Can V<5L?. No.
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CL, V and k Clearance (CL, units=L/hr) = Blood Volume of Drug Remove/hr Volume Distribution (V, units=L) What does k = 0.5 /hr mean?
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CL, V and t 1/2 Time in which the [drug] is half the initial [drug]
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Total CL, AUC and V Dose (mg) = CL (L/hr) * AUC ((mg*hr)/L) – IV bolus
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Things you learned Fractional elimination rate constant (k) Half-time (t 1/2 ) Mean residence time (MRT) Extraction ratio (E) Amount of Drug (A) Volume distribution (V) Clearance (CL)
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