Title 18. EFFECT OF HEPATIC DISEASE ON PHARMACOKINETICS.pdf ✅

PHARMD GURU Page 2  A few tests have been used to relate the severity of hepatic impairment to predicted changes in the pharmacokinetic profile of a drug.  Examples of these tests include the ability of the liver to eliminate marker drugs such as antipyrine, indocyanine green, monoethylglycine-xylidide, and galactose.  Furthermore, endogenous substrates, such as albumin or bilirubin, or a functional measure, such as prothrombin time, have been used for the evaluation of liver impairment. DOSAGE CONSIDERATIONS IN HEPATIC DISEASES:  Several physiologic and pharmacokinetic factors are relevant in considering dosage of a drug in patients with hepatic disease (Table 24-10).  Chronic disease or tissue injury may change the accessibility of some enzymes as a result of redirection or detour of hepatic blood circulation.  Liver disease affects the quantitative and qualitative synthesis of albumin, globulins, and other circulating plasma proteins that subsequently affect plasma drug protein binding and distribution.  As mentioned, most liver function tests indicate only that the liver has been damaged; they do not assess the function of the cytochrome P-450 enzymes or intrinsic clearance by the liver.