Nonlinear Pharmacokinetics Flashcards
Nonlinear PK
- Drug concentrations are ___ to the dose or become so over time
- Dose or Time ___ kinetics
- PK parameters change (6)
- priciples of ___ do not apply
- ___ process
- disproportional
- dependent
- t1/2, kel, CL, Vd, F, CL
- superposition
- saturable
Examples of Saturable Processes (graphs)
- dissolution
- metabolism
- facilitated transport
- plasma protein binding
Absorption Mechanisms
- ___ transport in the gut wall
- ___ metabolism
- drugs with ___ solublity in GI given in relatively ___ dose
- saturable gastric or GI ___
- saturable
- intestinal
- low, high
- decomposition
Distribution Mechanisms
- saturable ___ binding
- cellular uptake
- tissue binding
- CSF transport
- saturable transport in or out of tissues
- plasma protein
Renal Elimination Mechanisms
- ___ sectretion
- tubular ___
- change in ___ pH
- active
- reabsorption
- urine
Metabolism Elimination Mechanisms
- ___ metabolism
- cofactor/enzyme ___
- ___ induction
- altered ___ blood flow
- metabolite inhibition
- saturable
- limitation
- enzyme
- hepatic
Michaelis-Menten Model - Vmax and Km
T or F: KM and Vmax are dependent on the nature of the drug and the enzymatic process involved.
True
Michaelis-Menten Model - Vmax and Km
What does the non linear equation look like?
Michaelis-Menten Model - Vmax and Km
When Cp«Km
___ order
first
Michaelis-Menten Model - Vmax and Km
When Cp»Km
___ order
zero
rate = Vmax
Phenytoin
- anticonvulsant/antiepileptic
- ___ therapeutic index
- CNS adverse effects are ___ dependent
- CYP___ substrate
- Metabolic capacity ___
- change in dose is ___ to ss plasma concentrations
- narrow
- concentration
- CYP2C9
- limited
- disproportionate
loading dose equation
S x F x Dose = Vd x Css,desired
Saturable processes
- ___ drug absorption: Saturable ___ transport
- Drug distribution: Saturable protein binding of ___
- Drug metabolism: Saturable metabolism of ___
- Drug excretion: Active secretion of ___
- Active, gut wall
- salicylates
- phenytoin
- penicillin G
the elimination or absorption kinetics are nonlinear and may be a combination of ___ and ___ processes.
zero and first order
The half-life ___ with increased dose due to saturation of an enzyme/transporter system important for drug elimination or absorption
increases
