Gibaldi M
Am J Med. 1977 Apr;62(4):471-4. doi: 10.1016/0002-9343(77)90399-0.
Plasma protein binding of many drugs is impaired in patients with renal disease. This often results in a larger apparent volume of distribution and a larger clearance of the drug compared to that observed in patients with normal renal function. Hence, renal disease can also influence the pharmacokinetics of drugs that are eliminated from the body by biotransformation rather than by renal excretion, Repetitive administration of a given dose of a drug that is eliminated from the body by nonrenal mechanisms may result in considerably lower steady-state concentrations of total drug in the plasma of patients with renal disease than in that of patients with normal renal function. On the other hand, in the absence of liver disease, the average steady-state serum concentration of free (unbound) drug is likely to be the same in both groups of patients. For this reason, it is probably not necessary to change the usual daily dose of a drug that is eliminated from the body by nonrenal mechanisms when it is given to a patient with renal disease. However, such drugs should be administered in divided doses to minimize adverse effects.
