英国纽卡斯尔大学 药理学课件9

Basic pharmacokineticsห้องสมุดไป่ตู้
Professor F Kamali Wolfson Unit of Clinical Pharmacology
Basic pharmacokinetics
Pharmacokinetics concept One compartment model SemiSemi-logarithm drug concentration v time plot Measurement of drug pharmacokinetic parameters
Calculation of AUC
Calculation of CL from AUC
Amount eliminated = CL x AUC Dose = CL x AUC Since dose and AUC are known Then: CL can be calculated
Basic pharmacokinetics
What is 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 concentration:above processes taking place simultaneously.
CL = Rate of elimination (mg/min) C (mg/ml)
CL units in ml/min
Determination of clearance
Trapezoidal method Over a small time, δt, the amount of drug eliminated: = CL. C. δ t
Factors affecting drug pharmacokinetics
Patient characteristics: Age Sex Total body weight Smoking habits Alcohol consumption Other co-ingested drugs co-
Slope = a/b
a b
2. Equation Kel= 0.7 (time)-1 t½
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) α C (dC/dt) Rate of elimination = CL x C Hence:
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.
SemiSemi-logarithm plot
SemiSemi-logarithm plot
Calculation of drug half-life (t½) half(t½)
Calculation of elimination constant (Kel)
Two methods
1.
Gradient method
SemiSemi-logarithm plot
A Kel of 0.1/h implies 10% of drug eliminated per hour. -Kel=slope =1n C1-1nC2/t C1Rewrite 1n C1–1n C2 as: C1– 1n (C1/C2) When time interval t=t½; t=t½; C1/C2=2 As 1n 2 = 0.693 Kel = 0.693 t½
What is the value of pharmacokinetics?
Establish and maintain therapeutic, yet nonnontoxic 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.
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
Factors affecting drug pharmacokinetics
Disease states: Liver disease (cirrhosis, hepatitis) Renal disease Congestive heart failure Infection Fever Shock Severe burns Anaemia