Estimate Elimination Rate Constant - Example Calculations

Effect of Renal Function on Drug Excretion

A female patient is to receive Drug7 and it is known that the elimination of this drug depends on renal function. The creatinine clearance was measured from a timed urine collection over 10 hr and a serum concentration measured at the midpoint of the urine collection period. The urine volume collected was 646 ml and the creatinine concentration in this sample was 38.68 mg/dl. The midpoint creatinine serum concentration was 0.56 mg/dl. Determine the creatinine clearance using the urine/plasma data. Once you have the calculated creatinine clearance for this patient estimate the expected elimination rate constant for Drug7 in this patient.

From a literature reference you find the following data [Derived from Ritschel, 1980]

Drug Name Slope Intercept
Drug10.005250.07
Drug20.0065170.138
Drug30.0043920.093
Drug40.006370.7056
Drug50.0001890.1033
Drug60.0007250.493
Drug70.0026250.035
Drug80.0039750.053
Drug90.0035060.2072
Drug100.0063710.6255
Drug110.0013290.1305
Drug120.0003850.0308
Drug130.0009180.0058


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Some Equations:

kel =

Equation 27.1.1 Elimination rate constant calculated from creatinine clearance


Estimate CrCl from urine collection

Equation 27.1.2 Creatinine Clearance calculated from a timed urine collection

UCr is the concentration of creatinine in urine in mg/dl, Vu is the volume of urine in ml, SCr is the serum creatinine concentration in mg/dl and t is the collection time in minutes.


Cockcroft and Gault equation for CrCl

Equation 27.1.3 Cockcroft and Gault equation for estimating Creatinine Clearance

Weight in kg and SCr is the serum creatinine concentration in mg/dl. Note, you should only multiply by 0.85 in the case of female patients. The original authors of this equation used actual body weight in Equation 27.1.3. 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, p4).

IBW (male) (kg) = 50 + 2.3 x (Ht(in) - 60) or IBW (female) (kg) = 45.5 + 2.3 x (Ht(in) - 60) (Murphy, 2001, p4-5)


References
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