Tiêu đề 16. DOSE ADJUSTMENT FOR UREMIC PATIENTS.pdf ✅

PHARMD GURU Page 1  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.  Whether renal impairment will alter the pharmacokinetics of the drug enough to justify dosage adjustment is an important consideration.  For many drugs that are eliminated primarily by metabolism or biliary secretion, uremia may not alter pharmacokinetics sufficiently to warrant dosage adjustment. Active metabolites of the drug may also be formed and must be considered for additional pharmacologic effects when adjusting dose.  For some drugs, the free drug concentrations may need to be considered due to decreased or altered protein binding in uremia.  Combination products that contain two or more active drugs in a fixed-dose combination may be differentially affected by decreased renal function and thus, the use of combination drug products in uremic patients should be discouraged.  The following methods may be used to estimate initial and maintenance dose regimens. 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 over time. 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, 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. 16. DOSE ADJUSTMENT FOR UREMIC PATIENTS
PHARMD GURU Page 2  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 non-renal drug clearance to be unchanged.  The fraction of normal renal function remaining in the uremic patient is estimated from Clcr.  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 for 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. NOMOGRAMS  Nomograms are charts available for use in estimating dosage regimens in uremic patients (Bjornsson, 1986; Chennavasin and Craig Brater, 1981; Tozer, 1974).  The nomograms may be based on serum creatinine concentrations, patient data (height, weight, age, gender), and the pharmacokinetics of the drug.  As discussed by Chennavasin and Brater (1981), each nomogram has errors in its assumptions and drug database.  Most methods for dose adjustment in renal disease assume that nonrenal elimination of the drug is not affected by renal impairment and that the remaining renal excretion rate constant in the uremic patient is proportional to the product of a constant and the Clcr:
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