Drug Dosing

In any patient in whom a rapid therapeutic response is needed, a loading dose must often be administered. As described earlier, selected drugs have altered Vd in CKD patients and consequently the loading dose must be modified from loading doses used in patients with normal renal function. Phenytoin and digoxin could be examples of when the loading dose used should be smaller than what might be used in non-CKD patients. In CKD patients, the maintenance dose regimens of many drugs are modified by extending the dosing interval since drug clearance is usually delayed in these patients. Extending the interval will extend the time for a drug to reach steady state (3-5 half lives) and may delay achieving therapeutic goals.

Typically, the dose of a renally eliminated drug is reduced and/or the dosing interval extended in patients with CKD. Whether one technique or the other is used depends on the pharmacodynamics of the drug. Drugs that require maintenance of a serum concentration over the dosing interval should be administered as often, but with reduced doses. Drugs for which specific peak serum concentrations must be achieved will be dosed with an extended interval.

Comprehensive drug dosing guidelines are available to the clinician to determine which technique should be used. However the accuracy of these dosing guidelines has recently been called into question. Vidal et al. [27] compared the renal drug dosing recommendations of four commonly used published references. They found a surprising amount of disagreement between the four references. For example each drug-dosing recommendation had a different description of renal impairment with little agreement among categories. The authors also found several instances in which one recommendation stated a drug required no dosage adjustment but another stated that the same drug was contraindicated in renal impairment.

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