10 • s ele ed c lini al c al ula ion 175 Since the oxymorphone ER tablets are to be given every 12 hours, the single dose can be calculated as:
30 1
2 mg oxymorphone ER
day
day doses
× =15 mg oxymorphone ER day/
T herefore, one 15-mg oxymorphone ER tablet should be given to this patient every 12 hours.
CASE IN POINT 10.26 t he u ual re ommended do e of bu orphanol ar ra e na al pray i one pray on aining 1 mg of drug, and he na al pray olu ion on ain he drug a a on en ra ion of 10 mg/mL. c al ula e (a) he volume of olu ion delivered wi h ea h do e; (b) he number of do e on ained in he 2.5-mL manufa urer’
on ainer; and ( ) he number of able , on aining 5 mg of hydro odone bi ar ra e and 300 mg of a e aminophen, needed o produ e he 1-mg do e of bu orphanol ar ra e.
176 Pharma euti al c al ulations
By the Jelliffe equation7,8: For males:
CrCl (Patient s age in years Serum creatinine in mg/dL
= 98 0 8− . × ’ − 20) For females:
CrCl = 0.9 × CrCl determined using formula for males By the Cockcroft-Gault equation9:
For males:
CrCl Patient s age in years Body weight in kg Serum creat
= − ×
×
(140 )
72
’
iinine in mg/dL For females:
CrCl = 0.85 × CrCl determined using formula for males
Example Calculations of Creatinine Clearance
(1) Determine the creatinine clearance rate for an 80-year-old male patient weighing 70 kg and having a serum creatinine of 2 mg/dL. Use both the Jelliffe and Cockcroft-Gault equations.
By the Jelliffe equation:
CrCl mg dL
mg dL mg
= − × −
= − ×
= −
98 0 8 80 20 2
98 0 8 60 2
98 48 2
. ( )
( / ) ( . )
( / ) ( / ddL ) = ( / )mg dL
=
50 2
25 mL /min By the Cockcroft-Gault equation:
CrCl = − mg dL×
×
= ×
=
=
( )
( / )
.
140 80 70 72 2
60 70 144 4200
144
29 2 mL / min
(2) A 70-year-old gentleman and his 68-year-old wife have their annual physical exams. He weighs 160 lb and she 126 lb. His blood work reveals a serum creatinine of 1.3 mg/dL and hers is 1.1 mg/dL. Using the Cockcroft-Gault equation, calculate their respective creatinine clearance rates.
H is CrCl H er CrCl
= − ×
× =
= × −
( ) .
. .
. (
140 70 72 7 72 1 3
0 85 140 68
54 4 mL / min )) .
.× .
× 57 3 =
72 1 1 44 3 mL / min
10 • s l c l al c al ula o 177 Ad j Us t in G c r e At in in e c Le Ar An c e FOr b Od y s Ur FAc e Ar e A
It is sometimes desirable to adjust the calculated creatinine clearance for body surface area to account for this possible variable in determining drug dosage. T his adjustment is accomplished through the use of a nomogram or equation to determine body surface area (BSA), as described previously in Chapter 8, and the following formula:
BSA CrCl Adjusted CrCl 1 73. × =
If a patient weighing 120 lb and measuring 60 inches in height has a calculated creatinine clearance of 40 mL/min, adjust the CrCl based on body surface area.
U sing the nomogram in Chapter 8, the patient’s BSA is determined to be 1.50 m2. 1 50
1 73 40
2 2
.
. m / min . ,
m × mL = 34 68 mL / min adjusted CrCl
N ormal CrCl may be considered 100 mL/min. T hus, in the preceding example, the patient would exhibit about 35% of normal creatinine clearance.
Us e OF c r e At in in e c Le Ar An c e in d e t e r min in G d Os e s
T he CrCl method for determining drug dose is used with various drugs in which renal func- tion is a factor. Meperidine, for example, is dosed based on creatinine clearance as follows:
CrCl = 10 − 50 mL/min, give 75% of usual dose CrCl < 10 mL/min, give 50% of usual dose
T he patient in example problem 2 on page 174 has a serum creatinine of 2.4 mg/dL. Using the Cockcroft-Gault equation, determine if the meperidine dose should be adjusted for kidney function.
212 1
2 2 96 36 140 57 96 36
72 2 4 46 29
lb kg
lb kg
CrCl mL
× =
= − ×
× =
. .
( ) .
. . / minn
According to the dosing information, 75% of the dose should be given. Since the dose calculated in example problem 2 on page 174 is 200 mg, the patient should receive 200 mg × 75% = 150 mg based on his renal function.
For certain drugs, tables of dosage guidelines may be presented in the labeling/
literature to adjust for impaired renal function. For example, the usual dose of the anti- infective drug ceftazidime is 1 g every 8 to 12 hours, with dosage adjusted based on the location and severity of the infection and the patient’s renal function. For adult patients with impaired renal function, guidelines for dosage based on creatinine clearance are given in Table 10.5.
Using Table 10.5, determine the dose and daily dose schedule for a 62-year-old female patient weighing 70 kg with a serum creatinine of 1.8 mg/dL.
CrCl = × − × mL
× =
0 85 140 62 70
72 1 8 35 81
. ( )
. . / min
According to the table, a patient with a creatinine clearance of 31 to 50 mL/min should receive a dose of 1 g every 12 hours.
178 Pharma euti al c al ulations
Tab e 1 0 .5 • CREATININE Cl EARANCE d OSING GUId El INES FOR CEFTAz Id ImE (Iv OR Im)a
Rena Function
Creatinine
C earance ( l / in) d ose Frequency
Normal to mild impairment 100–51 1 g q8–12 h
Moderate impairment 50–31 1 g q12h
Severe impairment 30–16 1 g q24h
Very severe impairment 15–6 500 mg q24h
Essentially none <5 500 mg q48h
aAdapted from product literature for FORTAZ (ceftazidime). Available at http://www.access- data.fda.gov/drugsatfda_docs/label/2014/050578s055,050634s023lbledt.pdf. Accessed February 23, 2015.
CAl CUl ATIONS CAPSUl E Creatinine Clearance Equations
7–9Jelliffe equation For males:
CrCl 98 0.8 (Patient’s age in years 20) Serum creatinine in mg/dL
= − × −
For females:
CrCl 0.9 CrCl determined by equation for males= × Cockcroft-Gault equation
For males:
CrCl (140 Patient’s age in years) pt. wt., kg 72 Serum creatinine
= − ×
× iin mg/dL
For females:
CrCl 0.85 CrCl determined using for males= × Adjusting CrCl for body surface area
BSA
1.73 × CrCl Adjusted CrCl=