In Figure 23-7 from Cecil (1992) page 90, the dose fraction 0 of Harrison is:
(1) the percentage of nonrenal elimination to total normal elimination
(2) the percentage of a dose to give
(3) the percentage of normal drug clearance remaining)
dose fraction =
= [kri] / [k]
dose to give for a degree of renal impairment =
= (usual dose with normal renal function) * (dose fraction)
where:
• kri is the fractional rate constant for elimination in renal failure
• k is the fractional rate constant for elimination in normal renal function
The normal renal clearance is taken to be 100 mL/min. The patient's creatinine clearance can be estimated from serum creatinine.
dose fraction at patient's creatinine clearance =
= (((1 - (dose fraction for CrCl=0)) / 100 * (patient's creatinine clearance)) + (dose fraction CrCl=0))
and
dose to administer to patient =
= (usual dose) * (dose fraction at patient's CrCl)
according to the usual dosing interval.
This approach assumes that the volume of distribution for a drug is not altered in renal failure. Another assumption is that the nonrenal k 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 k by one half. Plasma level monitoring is essential to guide dosage adjustments.
Nomogram with Dose Fraction vs Creatinine Clearance
The dose fraction can be derived from a nomogram. The plot of the dose fraction vs creatinine clearance is linear on both axes. The upper right corner of the nomogram is taken as (100,1.0); the point of crossing the y axis depends on the dose fraction when creatinine clearance is zero.
slope of line =
= ((1 - (dose fraction at 0 creatinine clearance)) / 100)
intersect of y axis =
= (dose fraction at 0 creatinine clearance)
dose fraction to give for a degree of renal failure =
= (creatinine clearance in mL/min) * ((1 - (dose fraction at 0 creatinine clearance)) / 100) + (dose fraction at 0 creatinine clearance)