In the case of diazepam it has been found that the percentage unbound could be correlated with age for females, but not males. Drug interactions based on protein binding, and other factors, can be more pronounced in the elderly because they tend to be taking more drugs. Cardiac output in the elderly is reduced, thus distribution to the kidneys and liver are expected to be reduced. For high extraction drugs this could alter the overall elimination of the drug. The liver is the major organ involved in metabolism and as shown in the table, liver blood flow and liver mass tend to decrease with age.
Protein binding also is reduced, especially to albumin, as mentioned in the previous section.
The third determinant of drug metabolism, intrinsic clearance is quite variable and dependent on the metabolic pathway. Acetylation appears to be unchanged with age, isoniazid clearance is not altered. Examples are lidocaine, phenytoin, propranolol, theophylline. Serum creatinine is also decreased with age because of the reduced muscle mass. However, the formulas presented earlier in the section on renal disease can be used to calculate creatinine clearance as a function of age and thus make dosage regimen adjustments.