英国纽卡斯尔大学药理学.ppt

Basic pharmacokinetics,Professor F Kamali Wolfson Unit of Clinical Pharmacology,Basic pharmacokinetics,Pharmacokinetics concept One compartment model Semi-logarithm drug concentration v time plot Measurement of drug pharmacokinetic parameters,Basic pharmacokinetics,Pharmacokinetics is a discipline that uses mathematical models to describe and predict drug amounts and concentrations in various body fluids that changes in these quantities over time. Absorption, distribution, biotransformation and elimination. Plasma drug concentration:- net results of the above processes taking place simultaneously.,What is pharmacokinetics?,What is the value of pharmacokinetics?,Establish and maintain therapeutic, yet non-toxic amounts of drug in body and at the pharmacologic site of action. More specifically: Rational choice of drug doses, frequency of administration, and route of administration.,Characteristics of the patient and his disease Can alter the pharmacokinetic properties of a drug Adjustment of dosage, dosing frequency can compensate for kinetic changes Problems of ineffectiveness and/or toxicity may be avoided. The understanding of pharmacokinetics should enhance the likelihood of safe and effective drug therapy.,Factors affecting drug pharmacokinetics,Patient characteristics: Age Sex Total body weight Smoking habits Alcohol consumption Other co-ingested drugs,Factors affecting drug pharmacokinetics,Disease states: Liver disease (cirrhosis, hepatitis) Renal disease Congestive heart failure Infection Fever Shock Severe burns Anaemia,One compartment model,Dye does not disappear at a steady rate Rate of elimination of dye is proportional to the concentration Any process in which the rate of change of a variable is proportional to the magnitude of that variable is said to be an exponential process,Semi-logarithm plot,A Kel of 0.1/h implies 10% of drug eliminated per hour. -Kel=slope =1n C1-1nC2/t Rewrite 1n C11n C2 as: 1n (C1/C2) When time interval t=t; C1/C2=2 As 1n 2 = 0.693 Kel = 0.693 t,Semi-logarithm plot,Semi-logarithm plot,Calculation of drug half-life (t),Calculation of elimination constant (Kel) Two methods,Gradient method 2. Equation Kel= 0.7 (time)-1 t,a,b,Slope = a/b,Elimination clearance (CL),Clearance used as a measure of elimination Applies to both excretion and metabolism Most drugs eliminated by first order kinetics Drug concentration Elimination,CL is the proportionality constant between the rate of elimination and concentration Rate of elimination (dC/dt) C Rate of elimination = CL x C Hence: CL = Rate of elimination (mg/min) C (mg/ml) CL units in ml/min,Determination of clearance,Trapezoidal method Over a small time, t, the amount of drug eliminated: = CL. C. t,Calc