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The importance of lipid solubility in membrane permeation

Routes by which solutes can traverse cell membranes

Theoretical partition of a weak acid (aspirin) and a weak base (pethidine) between aqueous compartments (urine, plasma and gastric juice) according to the pH difference between them.

The effect of urinary pH on drug excretion

The main routes of drug administration and elimination

The two phases of drug metabolism

Stimulation of hepatic metabolism of benzpyrene

The glucuronide conjugation reaction

Predicted behaviour of single-compartment model with continuous or intermittent drug administration

To achieve a steady state plasma concentration (Css) Drug entry = Drug exit Dosing rate = Excretion rate Dosing rate = Css x Clearance Clearance = Vd x ke Dosing rate = Css x (ke x Vd)/F ke = 0.693/ t1/2 Dosing rate = Css x (0.693 x Vd)/F
t1/2

t1/2 = 0.693 x Vd/Clearance = 0.693/ke

Drug T needs to be given intravenously: Clearance = 70 ml/min Desired plasma concentration = 3 mg/L Maintaenance dose = ????? Dosing rate = Clearance x Desired plasma concentration/F Dosing rate = 70 ml/min/1000 x 3 mg/L = 0.21 mg/min

Multiple Doses
Drug T needs to be given intravenously every 5 hours: Clearance = 70 ml/min Desired plasma concentration = 3 mg/L Dosing rate = Cl x Css x Dosing interval /F Dosing rate = 70 ml/min/1000 x 3 mg/L x (5hr) = 70 ml/min/1000 x 3 mg/L x (300 min) = 63 mg every 5 hours

Loading dose = ?????? Vd = 50 L Desired plasma concentration = 3 mg/L Loading dose = Vd x Desired plasma concentration = 3mg/L x 50L = 150 mg

Note: LD = 1.44 x Css x Vd (more accurate calculation) F

First Order Kinetics Rate of elimination is directly proportional to the drug cocentration dC/dt C dC/dt = -ke x C
(C1, t1) Cp Log Cp (C2, t2)

Time

Time

C2 = C1 x e -ke x t

C1 = C2 x e ke x t

t = t2 - t1

A patients acetaminophen level at 2:00 PM is 86.2 g/ml at 6:00 PM the same day is 27.8 g/ml ke = 0.283 h-1
What was the level at 10:00 AM?

C1 = C2 x e ke x t
C1 = 86.2 x e 0.283 x 4 C1 = 267.3 g/ml

A patients acetaminophen level at 2:00 PM is 86.2 g/ml at 6:00 PM the same day is 27.8 g/ml
What is Ke?

C1 = C2 x e ke x t ln 86.2 = ke x 4 27.8 ke = 0.283 h-1

C1 = e ke x t C2

ln C1 = ke x t C2

A patients acetaminophen level at 9:00 AM is 250 g/ml. What is the level at 5:00 PM the same day? (C2 = C1 x e -ke x t ) ke = 0.283 h-1
A. 27 g/ml B. 26 g/ml C. 252 g/ml D. 28 g/ml

If the t1/2 of drug T is 6 hrs. What would u expect the t1/2 of drug T to be in a patient with kidney failure?

A. < 6 hrs B. > 6 hrs C. = 6 hrs D. non of the above

Which of the following statements is CORRECT?

A. Weak bases are absorbed efficiently across the epithelial cells of the stomach B. Potency of a drug may be reduced if the drug is ionized at physiologic pH C. Alkalinization of the urine enhances the exretion of weak bases D. All of the above

The addition of glucuronic acid to a drug A. decreases the polar nature of the drug B. increases the rate of excretion of the drug C. is an example of a Phase 1 reaction D. involves cytochrome P-450

A drug, given as a 100 mg single dose, results in a peak plasma concentration of 20 g/ml. The Vd is: A. 0.5 L B. 1 L C. 2 L D. 5 L

Drugs showing zero-order kinetics of elimination

A. decrease in concentration exponentially with time B. show a plot of drug concentration versus time that is linear C. show a constant fraction of the drug eliminated per unit time D. Non of the above

Which of the following statements is CORRECT for a drug whose elimination from plasma shows first-order kinetics? A. The t1/2 of the drug is proportional to the drug conc. B. The amount eliminated per unit time is constant. C. The rate of elimination is proportional to the Cp D. A plot of drug concentration versus time is a straight line

If the Vd for the drug is small. This means that:

A. most of the drug is in the extraplasmic space B. higher dose can be tolerated C. most of the drug is in the plasma D. B & C

Induction of hepatic metabolizing enzymes

A. results in an increase in a drug t1/2 B. results in a decrease in the rate of cyt P450 synthesis C. leads to drug tolerance and the dosage may need to be increased D. All of the above

Assume that a drug has a t1/2 of 6 hrs. How long will it take for 87.5% of the drug to be cleared from the body? A. 6 hrs B. 12 hrs C. 18 hrs D. 24 hrsc

All of the following statements are correct EXCEPT?

A. Drugs with low partition coefficient are likely to to distribute in the plasma B. The more lipophilic a drug is, the lower is its partition coefficient C. Drugs with high partition coefficient will distribute in the adipose tissue D. A & C