1. McAuley, GlobalRPh Inc.

There are many problems encountered in writing a program to effectively dose a drug such as digoxin. It is inherently difficult because of such components as narrow therapeutic index, difficult to define therapeutic endpoints, inter and intra-patient variability,  and varying effects of pathological states and drugs on digoxin’s disposition.  In sum, there exists significant variability as far as a given dose and concentration produced in a given patient. It is important to be able to determine various patient attributes that may help predict drug concentrations for any given patient. There are several known attributes that have a direct correlation with the eventual therapeutic dose.       Variables such as ideal body weight, serum creatinine, age, concomitant drug therapy all have great influence on the eventual therapeutic dosing regimen.   The mathematical “backbone” of this program is based on the references below.  You will notice two sets of responses when using this program. The first result is based on the “Jelliffe” method which attempts to predict the percentage of digoxin eliminated in a 24 hour period and the dose of digoxin required to maintain the concentration in the therapeutic range. The other result is based primarily on the “Jusko equations (below) and “Koda-Kimble” which attempts to calculate the effective digoxin clearance.  After estimating the digoxin clearance, it is possible to make predictions regarding the steady state concentration:

Css  =  (Maint dose x F) /( dig cl  x  T)

F= bioavailability factor
T= dosing interval
dig cl= digoxin clearance obtained as noted above.
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The “Jusko” Dosing section is based on the following equations.

Initial dosing

1. Estimate Volume of Distribution (Jusko Equation)

Vd = 226 + [(298 x CrCl) / (29.1 + CrCl)] x (BSA / 1.73)
where CrCl = normalized creatinine clearance(ml/min)
BSA = Body surface area (square meters)

LD = Vd x Cp/F

where Vd = Volume of distribution (liters)

Cp = target serum level (mcg/l)
F = bioavailability factor:

• IV push = 1
· capsules= 0.95
· elixir = 0.8
· tablets = 0.75
1. Estimate Clearance (Koda-Kimble)

Cl = [(A x CrCl) + B] x C

where A = 0.88, for patient with Acute CHF, otherwise=1

B = 23, for patient with Acute CHF, otherwise=40
C = correction factor for interacting drugs:

• Quinidine = 0.65
· Spironolactone = 0.75
· Verapamil = 0.7
Other= 0.71
1. Calculate Maintenance Dose

MD = (Cl x Cp x tau) / F

where Cl = Clearance (liters/hour)

Cp = target serum level (mcg/l)
tau = dosing interval (hours)
F = bioavailability factor

Cpss = (MD x F) / (Cl x tau)

where MD = Maintenance dose (mcg)

F = bioavailability factor
Cl = Clearance (liters/hour)
tau = dosing interval (hours)

1. Estimate Volume of Distribution (Jusko Equation – see above)
2. Calculate digoxin clearance

Cl = [(MD x F) / Cp] / tau

where MD = Maintenance dose (mcg)

F = Bioavailability factor
Cp = Steady-state serum digoxin concentration (mcg/l)
tau = Dosing interval (hours)

1. Calculate Maintenance Dose

MD = (Cl x Cp x tau) / F

where Cl = Digoxin clearance (l/hr)

Cp = target serum level (mcg/l)
tau = dosing interval (hours)
F = bioavailability factor

Cpss = (MD x F) / (Kel x Vd x tau)

where MD = Maintenance dose (mcg)

F = bioavailability factor
Kel = Elimination rate (1/hours)
Vd = Volume of distribution (liters)
tau = dosing interval (hours)

These equations were provided by Rick Tharp of RXkinetics (https://www.rxkinetics.com). His site contains additional information on digoxin dosing as well as several other clinical areas.

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General info: