Tiêu đề 15. GENERAL APPROACH FOR DOSAGE ADJUSTMENT IN RENAL DISEASE & MEASUREMENT OF GLOMERULAR FILTRATION RATE AND CREATININE CLEARANCE.pdf ✅

PHARMD GURU Page 1 INTRODUCTION:  Several approaches are available for estimating the appropriate dosage regimen for a patient with renal impairment.  Each of these approaches has similar assumptions, as listed in Table 24-2.  Most of these methods assume that the required therapeutic plasma drug concentration in uremic patients is similar to that required in patients with normal renal function.  Uremic patients are maintained on the same after multiple oral doses or multiple IV bolus injections.  For IV infusions, the same Css is maintained. (Css is the same as after the plasma drug concentration reaches steady state.)  The design of dosage regimens for uremic patients is based on the pharmacokinetic changes that have occurred as a result of the uremic condition.  Generally, drugs in patients with uremia or kidney impairment have prolonged elimination half-lives and a change in the apparent volume of distribution.  In less severe uremic conditions, there may be neither edema nor a significant change in the apparent volume of distribution.  Consequently, the methods for dose adjustment in uremic patients are based on an accurate estimation of the drug clearance in these patients.  Two general pharmacokinetic approaches for dose adjustment include methods based on drug clearance and methods based on the elimination half-life. GENERAL APPROACH FOR DOSAGE ADJUSTMENT IN RENAL DISEASE
PHARMD GURU Page 2 MEASUREMENT OF GLOMERULAR FILTERATION RATE: Several drugs and endogenous substances have been used as markers to measure GFR. These markers are carried to the kidney by the blood via the renal artery and are filtered at the glomerulus. Several criteria are necessary to use a drug as a marker to measure GFR: 1) The drug must be freely filtered at the glomerulus. 2) The drug must neither be reabsorbed nor actively secreted by the renal tubules. 3) The drug should not be metabolized. 4) The drug should not bind significantly to plasma proteins. 5) The drug should neither have an effect on the filtration rate nor alter renal function. 6) The drug should be nontoxic. 7) The drug may be infused in a sufficient dose to permit simple and accurate quantitation in plasma and in urine. Therefore, the rate at which these drug markers are filtered from the blood into the urine per unit of time reflects the GFR of the kidney. Changes in GFR reflect changes in kidney function that may be diminished in uremic conditions. Inulin, a fructose polysaccharide, fulfills most of the criteria listed above and is therefore used as a standard reference for the measurement of GFR. In practice, however, the use of inulin involves a time consuming procedure in which inulin is given by intravenous infusion until a constant steady-state plasma level is obtained. Clearance of inulin may then be measured by the rate of infusion divided by the steady-state plasma inulin concentration. Although this procedure gives an accurate value for GFR, inulin clearance is not used frequently in clinical practice. The clearance of creatinine is used most extensively as a measurement of GFR. Creatinine is an endogenous substance formed from creatine phosphate during muscle metabolism. Creatinine production varies with age, weight, and gender of the MEASUREMENT OF GLOMERULAR FILTRATION RATE AND CREATININE CLEARANCE