DOSE ADJUSTMENT FOR UREMIC PATIENTS(5TH YEAR )

DOSE ADJUSTMENT FOR UREMIC PATIENTS

Dose adjustment for drugs in uremic or renally impaired patients should be made in accordance with changes in pharmacodynamics and pharmacokinetics of the drug in the individual patient. Active metabolites of the drug may also be formed and must be considered for additional pharmacologic effects when adjusting dose.

The following methods may be used to estimate an initial and maintenance dose regimen. After initiating the dosage, the clinician should continue to monitor the pharmacodynamics and pharmacokinetics of the drug. He or she should also evaluate the patient's renal function, which may be changing.

Basis for Dose Adjustment in Uremia

The loading drug dose is based on the apparent volume of distribution of the patient. It is generally assumed that the apparent volume of distribution is not altered significantly, and therefore that the loading dose of the drug is the same in uremic patients as in subjects with normal renal function.

The maintenance dose is based on clearance of the drug in the patient. In the uremic patient, the rate of renal drug excretion has decreased, leading to a decrease in total body clearance. Most methods for dose adjustment assume nonrenal drug clearance to be unchanged. The fraction of normal renal function remaining in the uremic patient is estimated from creatinine clearance.

After the remaining total body clearance in the uremic patient is estimated, a dosage regimen may be developed by (1) decreasing the maintenance dose, (2) increasing the dosage interval, or (3) changing both maintenance dose and dosage interval. Although total body clearance is a more accurate index of drug dosing, the elimination half-life of the drug is more commonly used for dose adjustment because of its convenience. Clearance allows for the prediction of steady-state drug concentrations, while elimination half-life yields information on the time it takes to reach steady-state concentration