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Maintenance Dosage Fraction Based on the Fractional Rate Constant

Description

If clearance data for renal failure is not available, then the fraction of the usual dose of drug required for patient with renal failure can be approximated by the ratio of the fractional rate constant for elimination from the body in renal failure to that with normal renal function. This ratio is then multiplied times the usual dose to get the dose needed in renal failure. Because the ratio gives the fraction of the usual dose to give for a degree of renal insufficiency, it is termed the dose fraction. The dose fraction (subscript 0) is the dose fraction when the creatinine clearance is 0.


 

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)

 


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Specialty

ICD-10