Management options:
(1) Use a smaller maintenance dose that is to be given at the usual dosage interval.
(2) Give the usual dose with a longer dosage interval.
While the average steady state plasma level can be equivalent with either approach, the fluctuation in plasma concentration are less if a reduced dose is given at the usual intervals, and so this is usually the preferred method.
This fraction of the usual dose can be determined based on either:
(1) drug clearance, or
(2) the fractional elimination rate constant (k).
Usually both renal clearance and the renal k are directly proportional to the creatinine clearance.
Whichever method is used, the calculations provide only a rough approximation, due to the individual variations in volume of distribution, metabolism and excretion. Plasma level monitoring is essential to provide the feedback essential for proper adjustment of the drug dosage.
normal drug clearance =
= ((normal renal clearance) + (normal nonrenal clearance))
In the presence of pure renal disease, nonrenal clearance is unaffected (ideally).
If normal renal creatinine clearance is 100 mL/min then:
estimated drug clearance =
= (estimated renal clearance) + (normal nonrenal clearance)
estimated renal clearance =
= (normal renal clearance for drug) * ((calculated creatinine clearance) / (100 mL/min))
adjusted maintenance dose =
= (regular maintenance dose) * ((estimated drug clearance) / (normal drug clearance))
This dosage should result in an average plasma concentration during the dosage interval that is the same as the average plasma concentration seen with that dosage interval but with normal renal function. The fluctuations between peaks and troughs will be less pronounced.
An assumption in the above calculations is that nonrenal clearance is constant in renal failure. Due to accompanying disorders, in many patients the metabolic clearance of drugs is reduced. When a drug with a narrow therapeutic index is used, an appropriate precaution is to reduce the value for nonrenal clearance by one half. Plasma level monitoring is essential to guide dosage adjustments.
