Estimate Elimination Rate Constant - Example Calculations

Effect of Renal Function on Drug Excretion

A female patient is to receive Drug1 and it is know that the elimination of this drug depends on renal function. The creatinine clearance was measured from a timed urine collection over 6 hr and a serum concentration measured at the midpoint of the urine collection period. The urine volume collected was 252 ml and the creatinine concentration in this sample was 78.51 mg/dl. The midpoint creatinine serum concentration was 2.4 mg/dl. Determine the creatinine clearance using the urine/plasma data information. Once you have calculated the creatinine clearance for this patient estimate the expected elimination rate constant for Drug1 in this patient.

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

Drug Name Slope Intercept

Drug1 0.00525 0.07
Drug2 0.006517 0.138
Drug3 0.004392 0.093
Drug4 0.00637 0.7056
Drug5 0.000189 0.1033
Drug6 0.000725 0.493
Drug7 0.002625 0.035
Drug8 0.003975 0.053
Drug9 0.003506 0.2072
Drug10 0.006371 0.6255
Drug11 0.001329 0.1305
Drug12 0.000385 0.0308
Drug13 0.000918 0.0058

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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. 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

Last update: Tue 2 May 2006 10:31:55 am

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Drug Name	Slope	Intercept
Drug1	0.00525	0.07
Drug2	0.006517	0.138
Drug3	0.004392	0.093
Drug4	0.00637	0.7056
Drug5	0.000189	0.1033
Drug6	0.000725	0.493
Drug7	0.002625	0.035
Drug8	0.003975	0.053
Drug9	0.003506	0.2072
Drug10	0.006371	0.6255
Drug11	0.001329	0.1305
Drug12	0.000385	0.0308
Drug13	0.000918	0.0058