Investigation of Pharmacokinetics in Special Populations

Once a drug is approved for marketing, it would be preferable if a single dosing regimen could be used for the vast majority of patients. However, there are many 

Biochemical indicators show only cell damage, not the amount of mass remaining. They provide only limited amounts of information about the ability of the liver to metabolize xenobiotic compounds such as drugs. 

There are no clear markers of liver dysfunction. Standard liver function tests such as rises in alkaline phosphatase and alanine aminotransferase (see Section 11.10.1) are only crude markers of liver function and have not proved useful in characterizing liver function in relation to drug pharmacokinetics. The effect of liver dysfunction on drug clearance is therefore often addressed descriptively rather than quantitatively (see Weeks and Tomlin, 2006, for further discussion). 

While renal contribution to overall metabolism is less than hepatic contribution, renal metabolism is of clinical importance. The kidney, in particular the renal cortex, contains many of the same metabolic enzymes found in the liver, including CYPs. Serum creatinine and creatinine clearance are the typical methods used to assess renal function, although 24-hour urine collection can also be used. These are reliable indicators of renal clearance. 

The elderly represent a growing proportion of the total population, and it is necessary to appreciate the age-associated physiological changes that occur in these patients and their effects on the disposition of drugs. 

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