Allie punke Pharmacokinetics tutoring Fall 2016 Introduction to Drug Disposition, Clearance, Volume of Distribution, and Intravascular Dosing Allie punke Pharmacokinetics tutoring Fall 2016

This is only to be used as a guide I am not involved in the selection of test questions. This is not to replace studying for the exam; only to supplement study. Just because it is discussed today does NOT mean it will be on the test. Just because it is omitted in this review does NOT mean it will be omitted from the exam.

Tips for Pharmacokinetics Learn the formulas! Know to go back and forth between each of them depending on the type of information you were given. Study especially hard for the first few exams…since the material will build on itself Make sure to always look at the units

Introduction to Drug Disposition Pharmacokinetics: What the body does to the drug Pharmacodynamics: What the drug does to the body Pharmacogenetics: Pharmacogenomics: Pharmacometrics:

ADME Absorption: Distribution: What are the two types? Passive and active Distribution: Acidic drugs bind to albumin, while basic drugs bind to alpha-1 acid glycoprotein True or False: A drug that has a high Volume of distribution (Vd) means that it is very hydrophilic. False, lipophilic

ADME Metabolism: Elimination: Which of the following is an example of a Phase II reaction? A. Hydrolysis B. Methylation C. Reduction D. Oxidation E. A and B What is the overall goal of liver metabolism? Intestinal metabolism affects absorption, while liver metabolism affects elimination. Elimination: Liver or kidney

Rate of Kinetics True or False: Zero-Order kinetics removes a constant fraction of drug Zero Order First Order Dependent on concentration? NOT dependent YES Constant amount or fraction removed? Amount Fraction

Rate of Kinetics Is this data an example of zero or first order? 215-182/215=15.3%, 182-149/182=18% Time (h) Concentration 215 2 182 4 149 6 116 8 83 10 50

Rate of Kinetics What would the graph of the previous table look like?

Clearance Clearance: The theoretical volume of blood from which drug is irreversibly removed per unit time Equations for Clearance: CL=k*V CL=Q*ER A patient is given 500 mg of a new drug. Plasma concentration entering the liver was 360 mg/L, and the concentration exiting the liver was 95 mg/L. (Assume liver blood flow is 81 L/h). What is the ER of the drug? 0.736 (360-95/360) Is it a high or low extraction drug? High What is the CL of the drug? 59.6 L/h CL=ERXQ, CL=k*V, ER=Cin-Cout/Cin

Clearance A patient is given 750 mg of a new drug. Plasma concentration entering the liver was 165 ng/L. The extraction ratio is 35%. What is the concentration leaving the liver? 107 ng/L 0.35=165-Cout/(165)

Clearance A patient is given 300 mg of a drug that has Vd of 75 L. Hepatic CL=900 ml/h, which is 60% of total CL. What is the total CL? Total CL*0.6=900 ml/h, 1500 ml/hr How much is renal CL, if it is 10% of hepatic clearance? 90 ml/hr What is the half-life of the drug? Half-life: 0.693/k CL=k*V 1.5 L/h=k*75 K=0.02 Half-life: 0.693/0.02=34 hours, Css=170 hours

Basics of CL and Vd True or False: If CL is increased, then Vd is also increased. CL=k*V How many half lives does it take to reach steady state? Calculating time to steady state: If k=0.0144 h-1, then 241 hours to reach steady state Css occurs when concentration in is equal to concentration out Css equation=DR/CL Css= D/CL

Intravascular Dosing What is the initial concentration if 1000 mg of drug (Vd=0.7 L/kg) is given to a patient (90 kg) via IV bolus? Co=D/V=1000 mg/(63 L)=15.8 mg/L When would you expect to see the maximum/peak concentration? Immediately!

Intravascular Dosing Calculate the elimination rate constant and the half-life of the drug. 1. Elimination rate constant: Ln(1.07/0.342)/8 hours=0.143 h-1 2. 4.85 hours Time (hr) Concentration 2 1.07 mcg/mL 10 0.342 mcg/mL

Intravascular Dosing A drug is given to a patient and at hour 2 and 9, the concentrations are 70 mg/L and 40 mg/L. What is the half-life? 8.68 hours K=0.0799 h-1 What is the initial concentration and concentration at hour 7.5. Co=D/V, Ct=Co^e-kt, 40=Coe^-0.0799*9=82 mg/L Ct=82 mg/L*e^-0.0799*7.5=45.1 mg/L How long will it take (starting from the time the drug was given) for the drug concentration to reach 2.5 mg/L? 2.5=82 mg/L*e^-0.0799*t, t= 43.7 hours

Intravascular Dosing What is the Vd (assume the dose was 2 grams)? Vd=24.39 L (82 mg/L=2000 mg/V) What is the CL? 1.94 L/h What is the AUC? AUC=Co/k=1027 mg*h/L AUC=D/CL= *Remember, there are 2 ways to calculate AUC.

Intravascular Dosing After an IV Bolus of 100mg of a drug, what is the area under the curve? What are the correct units for AUC? Given k = 0.186 h-1 and Co = 6.0 mg/L 32.26 mg*hr/L AUC=Co/k AUC=D/CL=100 mg/ CL=k*V 6 mg=100 mg/V

Questions? apunke@uthsc.edu Enjoy your weekend!