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PK & Biostatistics workshop 2010 schedule

Pharma Edge Centre (I) Pvt. Ltd.

Evaluation of basic Pharmacokinetic parameters and confidence intervals from data obtained during bioequivalence study using Excel worksheet

Day 1

8:30-9:00 a.m.

8:30-9:00 a.m.

Introduction Welcome to the participants & speakers Inauguration of workshop

9:00-10:30 a.m.

 

Introduction to Pharmacokinetics in Drug Discovery and Development

Introduction to Pharmacokinetics in Drug Discovery and Development

Onset of action

Duration of action

Termination of action

Therapeutic range

Factors affecting extra vascular dose administration

Drug absorption

Drug distribution

 
 

Drug metabolism & excretion

• Drug metabolism & excretion

Drug disposition

Apparent volume of distribution, V = Dose/(Cp)0

Systemic clearance Renal Clearance Hepatic clearance Organ clearance

Elimination half life (t1/2) Origin of 0.693 in eq. t1/2 = 0.693/K

Elimination rate constant, Kele

 
= 0.693/K • Elimination rate constant, K ele     Tea BREAK (10:30-10:45 a.m.) 10:45-11:30 a.m
 

Tea BREAK (10:30-10:45 a.m.)

10:45-11:30 a.m

10:45-11:30 a.m

Introduction to Pharmacokinetic Models

Intravenous Bolus Kinetics General concept One compartment model Two compartment model Three or higher compartment model Zero & first order kinetics

PK & Biostatistics workshop 2010 schedule

Pharma Edge Centre (I) Pvt. Ltd.

11:30 a. m. – 1:00 p.m.

 

Bioavailability/Bioequivalence

Planning a bioequivalence study

Selection of proper design

• Selection of proper design

Importance of pilot study data

How to extract maximum information from a pilot study data

Calculation of sample size for a pivotal study from CVs of a pilot study

Selection of time points for different types of formulations, combinations & metabolite information.

Normal & semi log plots of time vs concentration for test and reference

Data analysis

Obtaining AUCs, AUC o to t, & AUC 0 to ,, Tmax, Cmax, Kabs, Kele, t1/2, etc. from available data

 

Statistics required for comparison

 

LUNCH (1:00-2:00 p.m.)

 

2:00-3:30 p.m.

Workshop 1

Plot of time vs concentration data on a

semi log graph sheet

Simple, easy, quick & accurate way of obtaining basic PK parameters

Simple, easy, quick & accurate way of obtaining basic PK parameters

Plotting time vs concentration data on a semi log graph sheet and calculation of PK parameters such as

(Cp) 0

Volume of distribution (V)

Slope = (-K/2.303)

kele

t1/2

Calculation of same data using Excel worksheet

Comparison of data obtained from graph, Excel and that obtained using WinNonlin.

PK & Biostatistics workshop 2010 schedule

Pharma Edge Centre (I) Pvt. Ltd.

3:30 -5:00 p.m. Workshop 2 Calculation of all pharmacokinetic parameters such as , AUC o
3:30 -5:00 p.m.
Workshop 2
Calculation of all pharmacokinetic parameters such as , AUC o to t, &
AUC 0 to ∞ , T max , C max ,, K abs , K ele , t 1/2 , etc. using normal excel worksheet
Example 1: Six subject data for two treatment, two period crossover study
1. Arranging the data for test & reference formulations in an excel sheet
Arrange data as obtained for period I and Period II
Input randomization codes (T or R) for each subject for both periods
Sort to segregate Test and Reference data
Tabulate the data in a suitable manner for further calculations
2. Obtaining log transformed data from normal data for all subjects
3. Obtaining mean concentration data for test and reference
4. Calculation of Cmax, Tmax etc. for normal and log transformed data
5. Calculation of Kele and t1/2 for log transformed data
6. Obtaining ratios for all above parameters
7. Obtaining statistical means, + SD & % CV for above parameters
8. Obtaining time vs concentration plots for individual subjects using normal and log transformed data
9. Obtaining time vs concentration plot using normal and log transformed mean concentration data for test
and reference
10. Inputting formula for Trapezoidal rule
11. Calculation of AUC0 to t for normal and log transformed data for each subject and each treatment using
trapezoidal rule
12. Calculation of mean area under the curve for each treatment
13. Calculation of AUC 0 to inf Using formula AUC 0 to inf = AUC o to t /kele
14. Tabulation of all PK parameters for test and reference
15. Comparison of parameters obtained using excel sheet and those obtained using WinNonlin

PK & Biostatistics workshop 2010 schedule

Day 2

Pharma Edge Centre (I) Pvt. Ltd.

9:00 – 11:00 am

Workshop 2 continued (to be worked out y participants)

Example 2: 12 subject data for two treatment, two period crossover study

Example 3: Analysis of data for urine collection study

11:00 – 11:30 am

Tea Break

11:30 01:00 p.m.

Introduction to biostatistics

Common statistical terms

 

Descriptive statistics

Inferential statistics

Types of Data: i. Numerical ii. Categorical

Measure of central tendency i. Mean, ii. Median & iii. Mode

Measure of dispersion i. Range, ii. Standard Deviation & iii. Skewness

t-test and ANOVA

Probability

Statistics in Bioequivalence

 

Parametric or nonparametric

Transformation of parameters

Experimental design Crossover or parallel

Confidence intervals and bioequivalence

 

Equations for calculation of confidence intervals

 

Sample size in bioequivalence trials

1:00 – 2:00 pm

LUNCH

2:00 3:30 pm

Workshop 3 Calculation of confidence Intervals

 

Calculation of confidence intervals for data obtained in examples 1, 2 & 3 using Excel and comparison with those obtained using SAS

3:30 – 4:00 pm

Tea Break

4:00 -5:00 pm

Participant feed back and Certificates Distribution

 

Question / answers Analysis of data from participants Case studies by participants