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problem solving
Dr Manukumar Shetty
Department of Pharmacology
UCMS & GTB Hospital
Delhi
overview
• INTRODUCTION
• PHARMACOKINETICS PARAMETERS
– Linear/non-linear PK
– Pharmacokinetics models
– Clearance
– Vd
– Half-life
– Bioavailability
• DRUG DOSING IN
– Renal & hepatic disease
– Dialysis
– Heart failure
– Obesity
- Time: ….min
Definition
• Clinical pharmacokinetics is the application of
pharmacokinetic principles to the safe and effective
therapeutic management of drugs in an individual patient.
CURACILLIN BETTERMYCIN
STEADY-STATE STEADY-STATE
Dose CONCENTRATIONS CONCENTRATIONS
(mg/L) (mg/L)
0 0 0
100 15 25
250 37.5 62.5
500 75 190
1000 150 510
A. 10 L
B. 20 L
C. 30 L
D. 200 L
3/0.15= 20L
Problem no - 03
A 20L
B 25L
C 50L
D 500L
A 20L
Problem no 4
Here we can calculate LD using infusion rate and elimination rate as well .
Pharmacokinetics models
• A basic type of model used in pharmacokinetics is the
compartmental model.
• Compartmental models are categorized by the number of
compartments needed to describe the drug's behavior in the
body.
• There are one- compartment, two-compartment, and
multicompartment models.
• The compartments do not represent a specific tissue or fluid
but may represent a group of similar tissues or fluids.
• These models can be used to predict the time course of drug
concentrations in the body
The one compartment
model linear assumes
that the drug in question
is evenly distributed
throughout the body
into a single
compartment.
• V= dose/Cp • V= dose/Cp
= 500/16= 31.3L =500/31= 16.1L
• Cl=kV= 90mL/mim • Cl=kV= 84mL/mim
Importance of two-compartment
models
• For many drugs, multicompartment kinetics may be
observed for significant periods of time.
• t1/2 = 0.693/ ke
= 0.693/0.081
= 8.6 hr
Bioavailability
• The fraction of the administered dose that is delivered to the
systemic circulation is known as the bioavailability for the
drug.
= 10mg/hr
When the elimination rate constant decreases, the infusion
rate must decrease proportionately to maintain the same
Css.
However, because the elimination rate constant is smaller (ie,
the elimination t 1/2 is longer), the time to reach C SS will be
longer
Problem no – 12*
V = VB + (fB/fT)VT
Agents with large volumes of distribution are not easily
removed from the body
Compounds with small volumes of distribution
(aminoglycoside, theophylline) usually high dialysis clearance
rates
• Concentration/time
graph for
tobramycin in a
hemodialysis
patient
Problem no - 15
32mg/L
8mg/L
15mg/L
• Compute pharmacokinetic parameters:
• Vd = D/(Cpostdose − Cpredose)
= 1000 mg/(65 mg/L − 15 mg/L)
= 20 L
ke = (ln C1 − ln C2)/∆t
= (ln 65 mg/L − ln 32 mg/L)/44 h
= 0.0161 /hr
t1/2 = 0.693/ke
= 0.693 /0.0161 /hr
= 43 h