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Since the oxymorphone ER tablets are to be given every 12 hours, the
single dose can be calculated as:
Therefore, one 15-mg oxymorphone ER tablet should be given to this
patient every 12 hours.
CASE IN POINT 10.2
6
The usual recommended dose of butorphanol tartrate nasal spray is one
spray containing 1 mg of drug, and the nasal spray solution contains the
drug at a concentration of 10 mg/mL. Calculate (a) the volume of solution
delivered with each dose; (b) the number of doses contained in the 2.5-mL
manufacturer’s container; and (c) the number of tablets, containing 5 mg
of hydrocodone bitartrate and 300 mg of acetaminophen, needed to
produce the 1-mg dose of butorphanol tartrate.
Dosage Calculations Based on Creatinine
Clearance
The two major mechanisms by which drugs are eliminated from the body are
through hepatic (liver) metabolism and renal (kidney) excretion. When renal
excretion is the major route, a loss of kidney function will dramatically
affect the rate at which the drug is cleared from the body.
With many drugs, it is important to reach and maintain a specific drug
concentration in the blood to realize the proper therapeutic effect. The initial
blood concentration attained from a specific dose depends, in part, on the
weight of the patient and the volume of body fluids in which the drug is
distributed.
The kidneys receive about 20% of the cardiac output (blood flow) and
filter approximately 125 mL of plasma per minute. As kidney function is
lost, the quantity of plasma filtered per minute decreases, with an
accompanying decrease in drug clearance. The filtration rate of the kidney
can be estimated by a number of methods. One of the most useful, however,
is the estimation of the creatinine clearance rate (CrCl) through the use of
the following empiric formulas based on the patient’s age, weight, and serum
creatinine (Scr) value. Creatinine, which is a breakdown product from
creatine produced in muscle metabolism, is generally produced at a constant
rate and in quantities that depend on the muscle mass of the patient. Females
usually have a lower serum creatinine than males due to less muscle mass.
Because creatinine is eliminated from the body essentially through renal
filtration, reduced kidney performance results in a reduced CrCl. The normal
adult value of serum creatinine is 0.5 to 1.7 mg/dL (the range varies with the
laboratory used as the reference source). The CrCl represents the volume of
blood plasma that is cleared of creatinine by kidney filtration and usually
expressed in milliliters per minute.
By the Jelliffe equation7,8:
For males:
For females: CrCl = 0.9 × CrCl determined using formula for males
By the Cockcroft-Gault equation9:
For males:
For females: CrCl = 0.85 × CrCl determined using formula for males
In addition to the Jelliffe and Cockcroft-Gault equations, other equations
are used to estimate creatinine clearance for special patient populations such
as pediatric patients and elderly patients.
10
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:
By the Cockcroft-Gault equation:
2. A 70-year-old man 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.
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Normal CrCl may be considered 100 mL/min. Thus, in the preceding
example, the patients would exhibit about 54% and 44% of normal
creatinine clearance, respectively.
Use of Creatinine Clearance in Determining Doses
The CrCl method for determining drug dose is used with various drugs in
which renal function is a factor. Cisplatin, for example, is dosed based on
creatinine clearance as follows:
LW is a 40-year-old female patient who is 5 feet 3 inches tall, weighs 124
pounds, and has a serum creatinine of 1.4 mg/dL. The initial dose of
cisplatin is 50 mg/m2 every 3 to 4 weeks. Using the Mosteller formula to
determine BSA and the Cockcroft-Gault equation to determine CrCl,
calculate the dose of cisplatin for this patient.
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.
TABLE 10.5 CREATININE CLEARANCE DOSING
GUIDELINES FOR CEFTAZIDIME (IV OR IM)
a
a
Adapted from product literature for FORTAZ (ceftazidime). Available at
https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/050578s062lbl.pdf. Accessed June 22,
2020.
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.
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.
CALCULATIONS CAPSULE
Creatinine Clearance Equations7–
9
Jelliffe equation
For males:
For females:
Cockcroft-Gault equation
For males:
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For females:
Dosage Calculations Based on Ideal Body Weight
and Adjusted Body Weight
The ideal body weight (IBW) provides an excellent estimation of the
distribution volume, particularly for some polar drugs that are not well
distributed in adipose (fat) tissue. The IBW may be calculated through the
use of the following formulas based on the patient’s height and gender.
For males:
IBW = 50 kg + 2.3 kg for each inch of patient height over 5 feet
or in pounds
110 lb + 5 lb for each inch over 5 feet
For females:
IBW = 45.5 kg + 2.3 kg for each inch of patient height over 5 feet
or in pounds
100 lb + 5 lb for each inch over 5 feet
Adjusted body weight may be used in calculating dosages for obese
patients using the following equation:
11
In the preceding equation “0.25 to 0.4” is a correction factor range to
multiply by the difference between ABW and IBW. If using 0.25 for the
correction factor, the term “25% adjusted body weight” is often used, or
“40% adjusted body weight” if 0.4 is used for the correction factor.
Clinical controversy exists over the use of actual body weight, IBW, or
an adjusted body weight to determine dosages, and specific references
should be consulted to determine the most appropriate dose for a patient.12–
14
Example calculations of ideal body weight and
adjusted body weight
1. Calculate the ideal body weight in pounds and kilograms for a male
patient weighing 164 lb and measuring 5 feet 8 inches in height.
2. Calculate the ideal body weight, in kilograms, for a female patient
weighing 60 kg and measuring 160 cm in height.
3. Calculate the ideal body weight and 25% adjusted body weight, in
kilograms, for a male patient who is 6 feet 1 inch tall and weighs 255
lb.
Therapeutic drug monitoring
Also termed drug therapy monitoring, this process often includes the
analysis of blood serum samples to ensure optimum drug therapy. This is
especially important for categories of drugs in which the margin between
safe and toxic levels is narrow. Data are available indicating these levels.
15
The drugs presented in this chapter are but a few of those requiring specific
types of dosing. Many other drugs, including aminoglycoside antibiotics
(gentamicin, tobramycin, amikacin), theophylline, digoxin, and warfarin,
require dosing based on plasma levels of the drug, specific laboratory values,
creatinine clearance, and IBW. Clinical reference sources should be
consulted when dosing drugs with specific and complex dosing parameters.
CASE IN POINT 10.3.
A
A 35-year-old male patient weighing 180 lb and standing 5 feet 8 inches
tall has been diagnosed with AIDS. His physician prescribes lamivudine
(EPIVIR) as a component of his treatment program and knows that the
dose of the drug must be adjusted based on the patient’s renal function.
Laboratory tests indicate that the patient’s serum creatinine is 2.6 mg/dL
and has held at the same level for 5 days.
a. Calculate the patient’s IBW and use in subsequent calculations if
the IBW is lower than the patient’s actual weight.
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b. Calculate the patient’s CrCl by the Cockcroft-Gault equation.
c. Select the appropriate dose of lamivudine from the dosing schedule:
a
Case in Point courtesy of Flynn Warren, Bishop, GA.
Clinical Laboratory Tests
It is common practice in assessing health status to analyze biologic fluids,
especially blood and urine, for specific chemical content. The clinical
laboratory tests used, known as chemistries, analyze samples for such
chemicals as glucose, cholesterol, total lipids, creatinine, blood urea nitrogen
(BUN), bilirubin, potassium, sodium, calcium, carbon dioxide, and other
substances, including drugs following their administration. Blood
chemistries are performed on plasma (the fluid part of the blood) or serum
(the watery portion of clotted blood). Depending on the laboratory
equipment used as well as patient factors (such as age and gender), the
“usual” amount of each chemical substance varies, with no single “normal”
value, but rather a common range. For example, the reference range of
glucose in serum is, by some laboratories, 65 to 115 mg/dL and that for
creatinine is 0.5 to 1.7 mg/dL.
Table 10.6 presents examples of the normal ranges of serum chemistry
values for some commonly analyzed blood components. The “conversion
factors” shown are used to convert the units most often used in the United
States to those of the International System. For example, a cholesterol
reading of 180 (mg/dL) may be recorded as 4.68 millimoles per liter
(mmol/L or mM).
TABLE 10.6 EXAMPLES OF NORMAL RANGES OF
SERUM CHEMISTRY VALUES
a
a
Normal values shown may vary between test laboratories and may be referred to as “reference,”
“healthy,” or “goal” values.
b
The International System generally expresses these in mmol (or other units) per liter.
Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein
(HDL-C), and total cholesterol (TC) are each measured in assessing a
patient’s risk for atherosclerosis.16 The greatest risk comes from the non–
high-density lipoprotein cholesterol (non–HDL-C), particularly in patients
with high serum levels of triglycerides (TG or TGR). In addition, certain
accompanying patient factors are considered added risk factors and affect the
LDL-C goal for a particular patient. These include personal and/or familial
history of coronary heart disease, atherosclerotic disease, diabetes,
hypertension, and cigarette smoking. Table 10.7 presents categories of
cholesterol and triglyceride blood levels. Furthermore, total cholesterol is
calculated by adding triglyceride level divided by five, HDL, and LDL
levels (i.e., TC = TG/5 + HDL + LDL).
TABLE 10.7 CATEGORIES OF CHOLESTEROL AND
TRIGLYCERIDE BLOOD LEVELSa,
b
a
National Heart, Lung, and Blood Institute. What do blood tests show? Lipoprotein panel. Available
at https://www.nhlbi.nih.gov/health-topics/blood-tests. Accessed June 26, 2020.
b
MedlinePlus (U.S. National Library of Medicine website). Triglycerides. Available at
https://medlineplus.gov/triglycerides.html. Accessed June 26, 2020.
There are two “cholesterol ratios” that are considered clinically relevant to
risk assessment for cardiovascular disease. One is the ratio of total
cholesterol to HDL cholesterol, the target being 5:1 or less. The other ratio
used in assessing risk is LDL:HDL, with the target being 3:1 or less.
17
Greater proportions of HDL are considered to lower risk of cardiovascular
disease. In addition, the percent reduction required to achieve a goal level of
LDL cholesterol may be calculated as the difference in values as a percent of
the current level. The difference in values is calculated by subtracting the
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1.
2.
patient’s desired LDL from the current measured LDL level, then dividing it
by the current LDL level.
Example calculations involving clinical laboratory
tests
1. If a patient is determined to have a serum cholesterol level of 200 mg/dL,
what is the equivalent value expressed in terms of millimoles (mmol)
per liter?
2. Calculate the TC:HDL ratio when the total cholesterol is 240 mg/dL and
the HDL cholesterol is 60 mg/dL, and identify if the ratio is within the
desirable range.
The ratio is less than the maximum desired level of 5:1.
3. If 160 mg/dL is a patient’s current LDL level and the desired level is 100
mg/dL, calculate the percent reduction required.
PRACTICE PROBLEMS
Heparin-Dosing Calculations
A hospital pharmacy order calls for 5000 units of heparin to be
administered to a patient, twice daily, subcutaneously, for the
prevention of thrombi. The pharmacist has on hand a vial containing
10,000 Heparin Units/mL. How many milliliters of the injection
should be administered for each dose?
A physician orders 1500 units of heparin to be administered by
intravenous infusion per hour. The pharmacy provides a heparin
intravenous bag containing 25,000 units of heparin in 250 mL of
D5W. How many milliliters should be administered per minute?
3.
4.
5.
6.
7.
A male patient weighing 76 kg is placed on heparin therapy for the
prevention of deep vein thrombosis after surgery.
18
a. How many milliliters of a heparin injection containing 5000 units/mL
should be administered for a loading dose of 80 units/kg?
b. What should be the infusion rate, in mL/h, using a solution that
contains heparin 25,000 units/500 mL, to administer 18 units/kg/h?
c. Six hours after heparin therapy is initiated, the patient’s aPTT is
found to be 75 seconds. Adjust the infusion rate, in mL/h, according
to the heparin protocol (Fig. 10.1).
A blood sample taken from a 113-lb patient 6 hours after heparin
therapy is initiated shows an aPTT of 24 seconds.19 Calculate (a) the
bolus dose and (b) the infusion rate, in mL/h, according to the heparin
protocol (Fig. 10.1).
Enoxaparin sodium (LOVENOX) injection, a low-molecular-weight
heparin, contains 150 mg/mL in 0.8-mL prefilled syringes. The
recommended dose for knee replacement surgery is 30 mg every 12
hours. How many milliliters of the injection should be administered
per dose?
Equianalgesic Dosing Calculations
A patient has been taking acetaminophen 300 mg with codeine 30 mg
(TYLENOL with CODEINE #3) tablets and wishes to switch to
acetaminophen/hydrocodone tablets due to nausea and constipation
caused by the codeine. The patient has been taking one tablet every 4
to 6 hours. What would be the most appropriate dose and dosage
regimen for the acetaminophen/hydrocodone tablets?
a. One 2.5-mg hydrocodone/325-mg acetaminophen tablet every 4
to 6 hours
b. One 5-mg hydrocodone/300-mg acetaminophen tablet every 4 to
6 hours
c. One 7.5-mg hydrocodone/300-mg acetaminophen tablet every 6
hours
d. One 10-mg hydrocodone/325-mg acetaminophen tablet every 6
hours
TC is a 52-year-old female patient who is receiving 0.5 mL of a 50
mcg/mL injection of fentanyl citrate (SUBLIMAZE) every 2 hours
following surgery to manage her pain. Her physician wants to change
to oral oxycodone hydrochloride given every 4 hours so she can be
discharged from the hospital. What strength of oxycodone
hydrochloride tablets should be used for this patient?
a. 20-mg tablets
b. 15-mg tablets
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