Enter patient data by clicking on a field and then entering the data.
To choose an age unit, click the drop-down selector and select the appropriate unit
for the patient: years, months, or days.
Acceptable Patient Data
Parameter
Acceptable Range
Age
1 day to 110 years
Height
35 to 213 cm
Weight
2 to 251 kg
Serum creatinine
0.3 to 22 mg%
Creatinine clearance is calculated using the Swartz equation for pediatric
patients. For adults, the Cockcroft & Gault adjusted body-weight equation is the default
method. The default method can be changed in the settings.
To select a drug model, tap the drop-down selector to choose from the available
drug models.
Tap the Clear button to clear the current patient data.
Tap the Calc button to display patient specific calculated parameters: Creatinine Clearance (CrCl), Lean Body Weight (LBW), Body Mass Index (BMI), and Body Surface Area (BSA).
Tap the View Model button to proceed to the next step.
This screen displays the population model and target values for your patient.
These individual patient parameters may be modified on this screen.
FYI, population model parameters should be modified on the Model editor screen.
The parameters shown on this screen are:
Parameter
Notes
Vd per kg
Volume of distribution in liters per kilogram
Dosing weight
Weight in kilograms used for the Vd calculation:
Vd = DW × Vd per kg
Kel (or CL) – Renal
Renal portion of the Kel or CL equation:
Kel (or CL) = Nonrenal + (CrCl × Renal)
Kel (or CL) – Nonrenal
Nonrenal portion of the Kel or CL equation
Targets
For Vancomycin, select either traditional Peak/Trough or targeted AUC dosing
Target peak level
mcg/mL
Peak time
Time in minutes after the infusion ends at which the peak level is targeted.
For Vancomycin, this should be set to 60 minutes to avoid the distribution phase.
Target trough level
mcg/mL
Infusion time
Length of infusion in minutes
To enter and plot a continuous infusion:
1. Set infusion length to 60 minutes.
2. Then, on the dose entry screen, set the interval to one hour.
Buttons
Tap the Return button to return to the previous screen.
Tap the Prospective button to calculate a dose using population model
parameters only, without serum level data.
Tap the Retrospective button to enter and analyze serum level data
for this model.
To select a method, tap the Select Method drop-down list.
Selection
Details
Steady-state peak/trough
Traditional steady-state trough before the dose and peak after the infusion.
Steady-state single point
A single steady-state level drawn at any time after the infusion using
Bayesian analysis. Available only in the paid version.
Steady-state 2- or 3-point
Two or three levels drawn after a steady-state dose.
First dose 2- or 3-point
Two or three levels drawn after the initial loading dose.
Non–steady-state 3-point
A non–steady-state trough before the dose and two levels after the dose.
Extended interval
A “random” level drawn 6 to 16 hours after a once-daily aminoglycoside dose.
Carefully review the screen when entering time values:
Some fields are in minutes and others are in hours.
Times are relative to either the start or end of the sample infusion—use caution.
Buttons
Tap Return to go back to the previous screen.
Tap Clear All to remove all entered data.
Tap Calculate to compute individualized pharmacokinetic
parameters from the serum level data. The system will check for major data
entry errors before proceeding.
The Sawchuk–Zaske method is a foundational approach for individualized dosage adjustment
of select antibiotics, particularly aminoglycosides such as gentamicin and vancomycin,
to achieve therapeutic concentrations while minimizing toxicity.
The equations used by this method are found below in the Formulas.section.
Bayesian
Bayesian analysis is optional for the steady-state peak/trough and steady-state
two- or three-point methods, and is always used for the steady-state
single-point method.
If three post-dose levels are entered with the Post-dose or First-dose methods,
the data are fit using least-squares linear regression.
Aminoglycoside Extended-Interval
Analysis of once-daily or extended-interval aminoglycoside regimens is similar to
that used by the Hartford nomogram. If a 5 mg/kg gentamicin dose is analyzed, the
Consensus Nomogram is used. If a 7 mg/kg dose is used, the original Hartford
Nomogram is applied.
There are some slight differences on this screen depending on chosen drug model and whether prospective or retrospective dosing.
Prospective dosing
When dosing aminoglycosides prospectively (before serum levels are available),
you may choose one of the following dosing methods:
Option
Description
PK
Pharmacokinetic dosing Adults: One-compartment dosing based on target peak and trough levels. Pediatrics: Initial dose is weight based.
EI
Extended-interval dosing
Available only for aminoglycosides. The dose is weight based and the interval is based on CrCl.
Often referred to as the Hartford nomogram. Note: EI dosing is available only in adults with CrCl > 30 mL/min.
Retrospective dosing
The PK or EI choice is disabled because the dosing method was selected when serum level data were entered.
Dose entry
An “ideal” dose is displayed. You then enter a practical dose and dosing interval.
Buttons
Tap Model to view patient-specific pharmacokinetic parameters
(Vd, Kel, etc.).
Tap mg/kg to view the selected dose in mg/kg per dose and mg/kg per day.
Tap Return to return to the previous screen.
Tap Graph to view a plot of predicted serum levels for the selected dose.
Tap Email to send the dosing recommendation by email.
The application copies the dose and model parameters into the body of an email,
which can be sent using the device’s default email app.
Tap the menu icon in the upper right of the screen. The icon is 3 vertical dots.
Settings
This menu selection provides access to the application’s default settings:
Default height and weight units:
cm/kg or in/lb
Default serum creatinine units:
mg/dL or IU
Default CrCl method for adults:
Cockcroft–Gault using adjusted body weight (C&G ABW)
Cockcroft–Gault using lean body weight (C&G LBW)
Cockcroft–Gault using total body weight (C&G TBW)
Cockcroft–Gault normalized (no weight)
Jelliffe 1973
Jelliffe multi step
Apply minimum serum creatinine:
Enable or disable this option; the selected state is configured in the setting below.
Minimum serum creatinine setting:
Enter the minimum SrCr used for adult CrCl calculations, if selected above.
Apply IDMS adjustments:
Enable or disable this option to apply an adjustment that aligns IDMS-calibrated
serum creatinine values with traditional assay measurements. Because the pharmacokinetic
models were developed using traditional creatinine assays, unadjusted IDMS values may
underestimate serum creatinine, leading to overestimation of creatinine clearance and
potentially excessive dosing recommendations.
IDMS settings:
Regression equation used to correlate IDMS with traditional SrCr.
This screen allows you to select from the following creatinine clearance methods.
Tap the drop-down list to select a creatinine clearance method.
Buttons
Tap the Select method drop down to select a creatinine clearance calculation method.
Tap the Copy button to apply the new CrCl value.
Tap the Cancel button to return to the patient data screen.
The following optional CrCl methods are for adults only. For more detailed discussion,
see the
RxKinetics web site.
Method
Notes
C&G ABW
Cockcroft and Gault method using adjusted body weight.
This is the default method. You may change the default method in the Settings dialog which is accessed via the main menu.
C&G LBW
Cockcroft and Gault method using lean body weight.
C&G TBW
Cockcroft and Gault method using total body weight.
This method tends to overestimate CrCl in larger patients.
C&G Normalized
Removes weight from the Cockcroft and Gault equation. Some find this useful
when body size differs substantially from average.
Jelliffe 1973
Weight is not used in this equation. This method may be useful in patients
whose body size differs substantially from average.
MDRD (abbreviated)
Derived from a large study of patients with a wide range of kidney function.
MDRD calculates GFR, which does not directly correspond to CrCl. It may be
more accurate for GFR estimation, but is not always ideal for pharmacokinetic
modeling, which is traditionally based on Cockcroft and Gault.
Salazar and Corcoran
Derived from a study of obese patients. Often recommended for obese patients
instead of standard equations.
The Drug Model Editor allows you to view and modify all drug model parameters.
You may also create your own drug models and maintain multiple models for the
same drug.
Lean Body Weight (LBW)
Devine adult method1
LBW = 45.5 + [ 2.3 × (60 - height in inches) ]
Add 4.5 kg for males
Body Surface Area (BSA)
Mosteller equation2
BSA = (HT × WT)2 / 3600 where
HT = height in centimeters
WT = weight in kilograms
Creatinine Clearance (CLcr)
Cockcroft and Gault method3
CLcr = [ Weight × (140 - Age) ] / (SCr × 72)
Decrease by 15% for females
Weight may be one of the following:
Lean body weight
Adjusted body weight
Adjusted BW = LBW + 30% of excess over LBW
Total body weight
Jelliffe Multi-Step Method5
1. Estimate urinary creatinine excretion rate (E)
E (males) = LBW × [29.305 - (0.203 × Age)]
E (females) = LBW × [25.3 - (0.18 × Age)]
LBW = lean body weight in kilograms
2. Correct E for nonrenal creatinine excretion
E = E × [1.035 - (0.0377 × SCr)]
SCr = latest or average serum creatinine
3. Correct E for rising serum creatinine
E = E - [4 × LBW × (SCr1 - SCr2)] / D
SCr1 = latest serum creatinine
SCr2 = earlier serum creatinine
D = days between measurements
4. Calculate CLcr
CLcr = (E × 0.12) / (SCr × BSA)
Jelliffe 19739
CLcr = 98 - [0.8 × (Age - 20)] / SCr
Decrease by 10% for females
MDRD Method6,7
CLcr = exp{ 5.228 - [1.154 × log(SCr)] - [0.203 × log(Age)] }
Decrease by 25.8% for females
Increase by 121% for African Americans
Schwartz Pediatric Method8
CLcr = (c × Ht) / SCr
Ht = height in cm
SCr = serum creatinine
c = 0.45 if age < 1 year
c = 0.55 if age 1–12 years
Prospective Population Model
Wagner linear method11
Kel = Knr + (Kr × CLcr)
Vd = Vdper × WtKg
Kel = total elimination rate
Knr = nonrenal elimination rate constant
Kr = renal elimination rate
Vd = apparent volume of distribution (L)
Vdper = population Vd per kg
WtKg = weight in kg
Serum Level Prediction
One-compartment intermittent infusion11
Peak = [Dose / (tinf × Vd × Kel)] × [(1 - e-Kel×tinf) / (1 - e-Kel×t)]
Trough = Peak × e-Kel×(t - tinf) where
Dose = chosen dose (mg)
t = chosen dosage interval (hours)
tinf = infusion time (hours)
Vd = volume of distribution (liters)
Kel = elimination rate constant
Serum Level Evaluation
Standard Sawchuk–Zaske Method12
Three or four non-steady-state measurements
Kel = ln(Cp2 / Cp4) / tdiff
Vd = [(Dose / tinf) × (1 - e-Kel×tinf)] / { Kel × [ Cp2 - (Cp1 × e-Kel×tinf) ] } where
Cp1 = trough before infusion
Cp2 = peak after infusion
Cp3 = midpoint after infusion (optional)
Cp4 = trough after infusion
tdiff = time between levels (hours)
t = dosage interval (hours)
tinf = infusion time (hours)
Dose = dose (mg) Exception: least-squares Kel used if three post-dose levels are available
First-Dose Sawchuk–Zaske13
Two or three levels after the first dose
Kel = ln(Cp1 / Cp3) / tdiff
Vd = [ (Dose / tinf) × (1 - e-Kel×tinf) ] / (Cp1 / e-Kel×t1)
Cp1 = post-infusion peak
Cp2 = midpoint (optional)
Cp3 = post-infusion trough
tdiff = time between levels (hours)
t1 = hours after infusion when peak drawn
tinf = infusion time (hours)
Dose = dose (mg) Exception: least-squares Kel used if three post-dose levels are available
Linear Least Squares Determination of Kel14
Used when three post-dose levels are available
Kel = [ (n × Sxy) - (Sx × Sy) ] / [ (n × Sx²) - Sx² ]
n = number of data points
x = hours post-infusion
y = ln(serum level)
Sx = Sx, Sy = Sy, Sxy = S(xy), Sx² = S(x²)
Bayesian Analysis15
Bayesian estimation begins with population values for Vd and Kel and adjusts them
using measured serum levels while accounting for variability in both population
parameters and assay error. Kel and Vd are chosen to minimize the Bayesian objective
function shown below:
Area Under the Curve (AUC)
Vancomycin exposure is expressed as the 24-hour area under the concentration–time curve (AUC).
Antibiotic Kinetics calculates AUC using two complementary approaches:
Pharmacokinetic method:
AUC = Total daily dose ÷ Clearance (CL).
This method reflects the patient’s elimination phase and corresponds to how published
AUC targets (400–600) were derived.
Trapezoidal method:
AUC is also calculated by numerical integration of measured serum concentrations:
This method is sensitive to sample timing, assay noise, and early distribution effects,
which can slightly overestimate true exposure.
When the two AUC estimates differ, the lower value is used for dose targeting.
This conservative approach minimizes the risk of vancomycin overexposure and nephrotoxicity
while remaining consistent with how AUC-based targets were established.
For a detailed discussion of AUC-guided vancomycin dosing, see the
RxKinetics web site.
Devine, B. Gentamicin therapy. Drug Intelligence & Clinical Pharmacy. 1974;8:650–656.
Mosteller, R.D. Simplified calculation of body surface area. New England Journal of Medicine. 1987;317(17):1098.
Cockcroft, D.W., & Gault, M.H. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41.
Salazar, D.E., & Corcoran, G.B. Predicting creatinine clearance and renal drug clearance in obese patients from estimated fat-free body mass. American Journal of Medicine. 1988;84(6):1053–1060.
Jelliffe, R.W., & Jelliffe, S.M. Estimation of creatinine clearance in patients with unstable renal function. Mathematical Biosciences. 1972;14:17–24.
Levey, A.S., Bosch, J.P., Lewis, J.B., Greene, T., Rogers, N., & Roth, D. A more accurate method to estimate glomerular filtration rate from serum creatinine. Annals of Internal Medicine. 1999;130:461–470.
Levey, A.S., Greene, T., Kusek, J.W., & Beck, G.J. A simplified equation to predict GFR from serum creatinine. Journal of the American Society of Nephrology. 2000;11:A0828.
Schwartz, G.L. A simple estimate of glomerular filtration rate in children. Pediatrics. 1976;58:259–263.
Bulmer, M.G. Principles of Statistics. Dover Publications; 1967.
Okamoto, M.P., Chi, A., et al. Comparison of two Bayesian pharmacokinetic programs for predicting serum gentamicin concentrations. Clinical Pharmacy. 1990;9:708–711.
1. What is the difference between the Vancomycin “aggressive” and “conservative” models?
Vancomycin demonstrates substantial interpatient variability in pharmacokinetic behavior; therefore,
no single model is appropriate for all patient populations. The two available models correspond
closely to the two most commonly used one-compartment pharmacokinetic models.
The aggressive model is reserved for patients without significant comorbidities.
The conservative model is a "go-slow" approach for patients with comorbities, including but
not limited to: older adults and those with high BMI, renal impairment, or variable fluid status,
2. Why does the creatinine clearance from Antibiotic Kinetics differ from a manual calculation?
Differences usually arise from the body weight and equation used. There is no universal agreement on the
optimal weight or equation for all patients. Antibiotic Kinetics includes multiple creatinine clearance
formulas so clinicians can choose the method most appropriate for their practice.
See:
Creatinine clearance and renal dosing.
3. Why is the default once-daily gentamicin dose 5 mg/kg instead of Hartford’s 7 mg/kg?
This recommendation is based on a consensus statement published in the June 1997 issue of the
International Journal of Clinical Pharmacology and Therapeutics.
See:
Once-daily dosing of aminoglycosides.
4. How should intramuscular gentamicin be dosed?
Enter an infusion time of 90 minutes, which reflects the average absorption time for IM aminoglycosides.
Peak levels should be drawn at least 90 + 15 minutes after injection.
5. Must steady-state analysis always be used?
No. When the three-point method is used, steady-state conditions are not required. A trough level may
be obtained prior to the upcoming dose, followed by a post-infusion peak and an intermediate post-dose
sample. The trough and peak are used to estimate the volume of distribution, while the two post-dose
concentrations are used to determine the elimination rate constant.
7. How do I enter and graph a continuous infusion?
First, ensure that the infusion length on the Model View screen is set to 60 minutes.
Then set the interval on the Dose Selection screen to 1 (one) hour.
