F and CL part 2 Flashcards
Extraction ratio
a ratio of drug eliminated by a drug-eliminating organ during single pass
efficiency of a drug-eliminating organ to eliminate a drug
values range from 0 to 1
drug-dependent parameter
Organ clearance
Q X E
volume of plasma from which a drug is completely eliminated by a drug-eliminting organ per unit time
units: L/h, ml/min
drug dependent parameter
Hepatic extraction ratio
a fraction of drug eliminated by liver during single pass
efficiency of liver to eliminate a drug
0 to 1
Hepatic clearance
QH X EH
Volume of plasma from which a drug is completely eliminated (removed) by liver per unit time
QH= 0.7 L/min physiological value
Eh and CLh
CLh= Eh x Qh
Eh= CLh/Qh
High Eh drugs > 0.7 low Eh drugs < 0.3
Low Eh drugs
warfarin
theophylline
high protein binding and low enzyme activity against a drug limit hepatic elimination
Increasing free fraction of warfarin would have significant effects on its Eh
CLh= fu x CLint
High Eh drugs
Verapamil
these drugs are good substrates of drug-metabolizing enzymes
increasing free fraction of verapamil would have insignificant effects of Eh
CLh=QH
CL intrinsic factor
it reflects the natural ability of the liver to metabolize a drug, independent of binding restrictions
it is a property of a drug, just as Vd, Kel, and CL
no upper limit
Large CLint rapidly metabolized by the liver
Small CLint take longer to be metabolized
CLint= Vmax/Km
Enzyme inducers
increase CLint of interacting drugs
Enzyme inhibiters
decrease CLint of interacting drugs
Factors affecting CLh
Hepatic Plasma Flow (QH)
* Decreased by disease states such as heart failure, liver disease;
drugs such as propranolol.
* Increased by food
Hepatic Enzyme Activity (CLint)
* Decreased by liver disease, dietary deficiencies, enzyme inhibiting
drugs such as cimetidine.
* Increased by enzyme inducing drugs such as phenobarbital,
rifampin, and environmental pollutants including polycyclic
