Round table: Principle of dosage selection for veterinary pharmaceutical products
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Round table: Principle of dosage selection for veterinary pharmaceutical products Bayesian approach in dosage selection. NATIONAL VETERINARY S C H O O L T O U L O U S E. D. Concordet National Veterinary School Toulouse, France . EAVPT Torino September 2006.

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Round table: Principle of dosage selection for veterinary pharmaceutical productsBayesian approach in dosage selection

NATIONAL

VETERINARY

S C H O O L

T O U L O U S E

D. Concordet

National Veterinary School

Toulouse,France

EAVPT Torino September 2006


Bayesian forecasting methods therapeutic drug monitoring

Bayesian forecasting methods = pharmaceutical productsTherapeutic drug monitoring


Why a bayesian forecasting method

Efficacy pharmaceutical products

Toxicity

Exposure

Why a bayesian forecasting method ?

Consequence of PK Variability :

the same dose gives different exposures


Why a bayesian forecasting method1

Efficacy pharmaceutical products

Toxicity

Exposure

Why a bayesian forecasting method ?

Consequence of PK Variability :

the same dose gives different exposures

We need to anticipate the "level" of exposure


How to predict exposure

Exposure pharmaceutical products

How to predict exposure ?


How to predict exposure1

POPULATION PK pharmaceutical products

Cannot be predicted with covariates

Need further information

Exposure

Covariate : e.g. Age

How to predict exposure ?


The bayesian approach

a priori pharmaceutical products information

A blood sample at this time

The bayesian approach

Same dose

animals with the same age

Probably a high exposure


The bayesian approach1

Probably a small exposure pharmaceutical products

A blood sample at this time

The bayesian approach

Same dose

animals with the same age

a priori information


The bayesian approach2

Exposure ? pharmaceutical products

A blood sample at this time

The bayesian approach

Same dose

animals with the same age

a priori information


Why population information is needed
Why population information is needed ? pharmaceutical products

Concentration

Exposure ?

Time

A blood sample at this time


The bayesian approach3

A blood sample at this time pharmaceutical products

The bayesian approach

Same dose

animals with the same age


The bayesian approach4

Frequency pharmaceutical products

Exposure

A blood sample at this time

The bayesian approach

Same dose

animals with the same age


The a posteriori distribution
The pharmaceutical productsa posteriori distribution

Distribution of exposure for animals that received the same dose

have the same age

have the same drug concentation at the sampling time

Frequency

Exposure

Maximum a posteriori (MAP)

= Bayesian estimate = most common exposure


The a priori information

Frequency pharmaceutical products

Exposure

The a priori information

Same dose

animals with the same age

A blood sample at this time


The a priori information1

Frequency pharmaceutical products

Exposure

The a priori information

Same dose

animals with the same age

A blood sample at this time


The a priori information2

Frequency pharmaceutical products

Exposure

The a priori information

Same dose

animals with the same age

A blood sample at this time


How to predict exposure2

Exposure pharmaceutical products

Covariate : e.g. Age

How to predict exposure ?

POP. PK


How to predict exposure3

Exposure pharmaceutical products

Covariate : e.g. Age

How to predict exposure ?

POP. PK + 1 concentration

POP. PK


How to predict exposure4

Exposure pharmaceutical products

Covariate : e.g. Age

How to predict exposure ?

POP. PK + 2 concentrations

POP. PK + 1 concentration

POP. PK


Problem of highly variable drugs
Problem of highly variable drugs ? pharmaceutical products

1st Administration: fixed dose

Concentration

A blood sample at this time

Time


Problem of highly variable drugs1
Problem of highly variable drugs ? pharmaceutical products

2nd Administration: same animal, same dose as 1st

Large inter-occasion variability

Concentration

A blood sample at this time

Time


How does it work
How does it work ? pharmaceutical products

A population model

jth concentration measured on the ithanimal

jth sample time of the ithanimal


How does it work1
How does it work ? pharmaceutical products

A set of concentrations on THE animal :

(t1, Z1), (t2, Z2), …

Maximize the a posteriori likelihood

Minimize


To summarize
To summarize pharmaceutical products

Bayesian forecasting can be useful for:

pets

touchy drugs (narrow therapeutic index)

It requires:

results of a pop PK study

some concentrations on the animal

a recent computer

Can’t work for large inter-occasion variability


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