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.

Introduction

Welcome to the participants & speakers

Inauguration of workshop

9:00-10:30 a.m.

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 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

Tea BREAK (10:30-10:45 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
• 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

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 to t, &

AUC 0 to ∞, Tmax, Cmax,, Kabs, Kele, t1/2, 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 Pharma Edge Centre (I) Pvt. Ltd.

Day 2

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