Kinetics Lecture 11-04 Part 25

Front 1

linear vs nonlinear processes

the rate of linear processes is:

Back 1

proportional to drug concentration

Front 2

linear vs nonlinear processes

the nonlinear process:

Back 2

dose-dependent: the rate is not proportional to the drug concentration

time-dependent: the rate parameters depend on time

Front 3

causes of nonlinearity

dose-dependent

Back 3

- saturation of enzymes or carrier systems
- substrate(drug) inhibition of enzymes or carrier systems

Front 4

causes of nonlinearity

time-dependent

Back 4

- induction of enzymes
- changing pathophysiology
- circadian rhythm

Front 5

pharmacogenomic considerations

the future role of personalized medicine is:

Back 5

to identify patients with low expression of critical enzymes, including enzymes that are easily saturated, by genomic profiling before the start of therapy

Front 6

saturable proteins

absorption

Back 6

1. intestinal transporters: apparent ka decreased and ke~

2. intestinal efflux pumps: apparent ka increased and ke ~

Front 7

saturable proteins

elimination

Back 7

3. metabolic enzymes (secretion transporters): apparent ka ~ but not as significant as previous and ke decreased

4. reabsorption transporters: apparent ka ~ but not as significant as previous and ke increase

** for 1-4: results are when saturated and compared to linear process with same dose

Front 8

plasma level vs dose

Back 8

see pg 2 all slide

Front 9

AUC vs dose

for linear AUC is:

Back 9

proportional to the dose

Front 10

AUC vs dose

in nonlinear AUC- dose line deviates from linearity at higher doses

Back 10

positive deviation- causes 2 and 3

negative deviation- causes 1 and 4

see slides

Front 11

saturable kinetics

low drug concentration, first order: rate=

Back 11

vm/km * cp

Front 12

saturable kinetics

high drug concentration, zero order: rate=

Back 12

vm

Front 13

practice consideration

saturable processes lead to:

Back 13

elimination that is slower than expected for the given dose