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Equation 16.7.1 Creatinine Clearance
with serum creatinine expressed as mg/100 ml and creatinine clearance as ml/min. Normal inulin clearance values are 124 ml/min for men and 109 ml/min for women (Documenta Geigy, 1970). Because of some small renal secretion of creatinine, normal values of creatinine clearance are slightly higher than GFR measured with inulin. Thus, normal creatinine clearance values are about 120 to 130 ml/min.
Various investigators have developed equations which allow calculation of creatinine clearance using serum creatinine values. Thus a single serum level may used when renal condition is stable. One commonly used equation is that of Cockcroft and Gault.
Equation 16.7.2 Creatinine Clearance
Females: Use 85% of the value calculated for males. CsCr is the serum creatinine concentration in mg/dl. The original authors of this equation used actual body weight in Equation 16.7.2. More recently it has been recommended that ideal body (IBW) be used in this equation unless the actual body weight (ABW) is less (Murphy, 2001). This is consistent with earlier the recommendation to use lean body weight in Equation 16.7.2 as creatinine is formed in muscle (Shargel and Yu, 1985).
Equation 16.7.3 Ideal Body weight (Murphy, 2001, p4-5)
More recent equations for estimating creatinine clearance are those recommended by the National Kidney Disease Education Program (NKDEP) for adults (from the MDRD study) and children (Original Schwartz equation) calculation.
The relationship between creatinine clearance and overall drug elimination can be easily seen by looking at plots of kel observed versus creatinine clearance.
Figure 16.7.1 Plot of kel versus CLCR (Dettli Plot)
These are often called Dettli plots.
Figure 16.7.1 shows the situation with considerable excretion as unchanged drug. i.e. fe between 0.3 and 0.7.
Figure 16.7.2 Dettli Plot (fe = 1)
In Figure 16.7.2 drug is excreted entirely as unchanged drug. i.e. fe = 1
Figure 16.7.3 Dettli Plot (fe = 0)
In Figure 16.7.3 drug is excretion only as metabolized drug. i.e. fe = 0
We can use this information to calculate initial dosage regimens for patients taking drugs with high (> 0.25) fe values. The first step is to estimate the creatinine clearance in the patient from their serum creatinine value. From a Dettli plot (kel versus CLcr) constructed from previous studies with this drug we can estimate the elimination rate constant in this patient. We can therefore calculate an optimum dose and dosing interval to achieve the desired average drug concentration or maximum or minimum drug concentrations. The Dettli plot may be built into a computer program or nomogram.
Figure 16.7.4 Dettli Plot Showing kel Observed versus CLcr
This is the plot shown before. In the references shown below there is information useful for calculating kel in patients with impaired renal function.
As an example these data could be used to calculate the kel for a patient with a CLcr of 10 ml/min compared a subject with normal renal function of 120 ml/min
kelpatient = knr + b • CLcr = 0.01 + 0.0024 x 10 = 0.01 + 0.024 = 0.034 hr-1
Compare this with the value for the normal subject: kel = 0.01 + 0.0024 x 120 = 0.298 hr-1
kelpatient = 0.03 + 0.0005 x 10 = 0.03 + 0.005 = 0.035 hr-1
Compare this with the value for the normal subject: kel = 0.03 + 0.0005 x 120 = 0.09 hr-1
kelpatient = 0.008 + 0.00072 x 10 = 0.008 + 0.0072 = 0.0152 hr-1
Compare this with the value for the normal subject: kel = 0.008 + 0.00072 x 120 = 0.0944 hr-1
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