### 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.

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 (see Renal Chapter).

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.

Nomogram: plot of dose fraction vs creatinine clearance

The nomogram for the dose fraction plotted versus creatinine clearance can be approximated by an equation, which can then be used for computation.

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 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)

Harrison's Principles of Internal Medicine: Table of Dose Fractions for Antibiotics

Each antibiotic has a different dose fraction and fractional rate constant for elimination.

Antibiotic

DF0

k

Amikacin

0.01

0.4

Amoxicillin

0.15

0.7

Ampicillin

0.1

0.6

Carbenicillin

0.1

0.6

Cephalexin

0.04

0.7

Cephaloridine

0.08

0.4

Cephalothin

0.02

1.4

Cephazolin

0.06

0.35

Chloramphenicol

0.8

0.3

Clindamycin

0.8

0.2

Cloxacillin

0.25

1.2

Dicloxacillin

0.5

1.2

Doxycycline

0.8

0.03

Erythromycin

0.7

0.5

Gentamicin

0.02

0.3

Isoniazid (fast acet)

0.8

0.5

Isoniazid (slow acet)

0.5

0.25

Kanamycin

0.03

0.35

Lincomycin

0.4

0.15

Methicillin

0.12

1.4

Minocycline

0.9

0.06

Nafcillin

0.4

1.2

Oxacillin

0.25

1.4

Oxytetracycline

0.2

0.08

Penicillin G

0.1

1.4

Polymyxin B

0.12

0.15

Rifampin

1.0

0.25

Streptomycin

0.04

0.25

0.45

0.7

Sulfamethoxazole

0.85

0.07

Tetracycline

0.12

0.08

Tobramycin

0.02

0.35

Ticarcillin

0.1

0.6

Trimethroprim

0.45

0.06

Vancomycin

0.03

0.12

where:

• DF0 = dose fraction 0 = estimated fraction of usual dose of drug required for a patient with a creatinine clearance of 0 = kri/k

• k =  average overall fractional elimination rate constant of a patient with normal renal function, expressed as per hour

• acet = acetylator status (isoniazid)

Cecil Textbook of Medicine: Renal Elimination Rate Constants, Nonrenal Elimination Rate Constants and Percent Nonrenal Elimination for Antibiotics

Overview:

Each antibiotic differs in the manner of its elimination, with some predominantly excreted by the kidney and others not.

Drugs > 80% Renal

Antibiotic

k-renal (per hour)

k-nonrenal (per hour)

per cent nonrenal

acyclovir

0.2

0.02

10

0.05

0.005

10

amikacin

0.3

0.01

5

amoxicillin

0.6

0.1

10

ampicillin

0.5

0.06

10

carbenicillin

0.5

0.05

10

cefamandole

0.84

0.04

5

cefazolin

0.3

0.02

5

cefoxitin

1.0

0.05

5

cephalexin

0.7

0.03

5

cephalothin

1.4

0.03

5

0.5

0.05

10

flucytosine

0.24

0.01

5

gentamicin

0.3

0.02

5

kanamycin

0.3

0.01

5

methicillin

1.2

0.15

10

moxalactam

0.3

0.02

5

penicillin G

1.3

0.1

10

polymyxin B

0.13

0.02

10

streptomycin

0.24

0.01

5

tetracycline

0.07

0.01

10

ticarcillin

0.6

0.06

10

tobramycin

0.3

0.01

5

vancomycin

0.12

0.003

5

Drugs 50-80% Renal

Antibiotic

k-renal (per hour)

k-nonrenal (per hour)

per cent nonrenal

cefotaxime

0.6

0.28

30

cephapirin

0.9

0.3

25

dicloxacillin

0.6

0.6

50

erythromycin

0.30

0.15

35

ethambutol

0.09

0.09

50

isoniazid (slow acetylators)

0.12

0.12

50

lincomycin

0.1

0.06

40

nafcillin

0.7

0.5

40

oxacillin

1.1

0.35

25

oxytetracycline

0.065

0.015

20

trimethoprim

0.03

0.03

50

Drugs < 50% Renal

Antibiotic

k-renal (per hour)

k-nonrenal (per hour)

per cent nonrenal

amphotericin B

0.01

0.02

70

chloramphenicol

0.02

0.3

80

clindamycin

0

0.25

100

doxycycline

0.005

0.03

80

isoniazid (fast acetylators)

0.1

0.4

80

minocycline

0

0.06

100

rifampin

0

0.25

100

sulfamethoxazole

0.01

0.06

85

Comparing Tables

Harrison's: DF0 = (kri) / (k)

• DF0 and k given; kri = DF0 * k = essentially nonrenal k

Cecil's: renal k and nonrenal k, rounded to 2 decimal places

• percent nonrenal = Harrison's DF0 * 100%, rounded to nearest 5%

Example: tobramycin

• Harrison's DF0 0.02 and k 0.35; kri = 0.007 = 0.01 rounded to 2 decimal places

• Cecil's k nonrenal 0.01