Estimate Elimination Rate Constant - Example Calculations

Effect of Renal Function on Drug Excretion

A male patient is to receive Drug5 and it is known that the elimination of this drug depends on renal function. This patient is 87.3 kg (192.1 pound), 184.5 cm (72.6 inches) height and 47 years old. The measured serum creatinine was 1.14 mg/dl. Calculate the creatinine clearance for this patient using the Cockcroft and Gault equation. (Note: Use ideal body weight if less than actual body weight). Once you have the calculated creatinine clearance for this patient estimate the expected elimination rate constant for Drug5 in this patient.

A previous study with Drug5 resulted in the following data.

kel (hr^-1) Creatinine
Clearance (ml/min)

0.1052 10
0.1128 50
0.126 120

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Some Equations:

Equation 27.1.1 Elimination rate constant calculated from creatinine clearance

Equation 27.1.2 Creatinine Clearance calculated from a timed urine collection

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

Equation 27.1.3 Cockcroft and Gault equation for estimating Creatinine Clearance

Weight in kg and S_Cr 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

Ritschel, W.A. 1980 Handbook of Basic Pharmacokinetics, 2nd ed., Drug Intelligence
Murphy, J.E. 2001 Clinical Pharmacokinetics, 2nd ed., ASHP, Bethesda, MD
Sarubbi, F.A. and Hull, H.H. 1978. Amikacin serum concentrations: prediction of levels and dosage guidelines, Ann. Intern. Med., 89, p 612-618

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kel (hr^-1)	Creatinine Clearance (ml/min)
0.1052	10
0.1128	50
0.126	120