Spring Intro 2023

Mike Kelly

Sparse sampling and Population PK modelling in Phase III

Low renal fcn

Dose

Cp

1

0

-

-1

Structural model

-

-2

-

-3

Statistical model

Covariate model

log(plasma Concentration) - log(plasma Concentration)

-4

0

5

10 10

15 15

20 20

0

5

Time after dose (h) i e after dose (h)

Description

Prediction

29

Pharmacokinetics in Phase IV

 Life cycle management opportunities  Additional disease indications  Combination therapies  Pediatrics  Different formulations  Change in manufacturing processes

 In scenarios where formulations or manufacturing processes change it may be necessary to re-assess bioavailability or bioequivalence i.e. demonstrate that two formulations have the same exposure within stringent limits

30

15