Aminoglycoside formulas

 

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The aminoglycoside model is not hard-coded into the program.  The parameters are found in the drug model database and are fully user-editable.  You can tailor each drug model to fit your patient population, or you can create your own models.  See the Edit drug models section of the help file for further information.

 

Traditional method

Initial dosing

 

1.   Calculate dosing weight (DW)        

DW = LBW + [(ABW - LBW) x CF]

where ABW = actual weight

LBW = lean body weight

CF = 40% correction factor for obesity

 

2.  Calculate loading dose  (LD)

 

LD = (Cpmax  x  Vd  x  kel x  tinf) / (1 - e-kel x  tinf)        

where Cpmax = Target peak

Vd = population volume of distribution (from 3i. below)

kel = population elimination rate (from 3ii. below)

tinf = length of infusion

 

3.   Determine initial maintenance dose (MD)

i.   Calculate volume of distribution (Vd)

Vd = 0.27 x DW

 

ii.  Calculate elimination rate (kel) from creatinine clearance

 

kel =  0.01 + (CrCl x 0.0024)

where CrCl =  creatinine clearance

 

iii.  Calculate ideal maintenance dose

 

MD = kel  x  Vd  x  Cpmax  x  tinf  x  (1 - e-kel x tau / 1 - e-kel x tinf)

where Cpmax = Target peak

Vd = population volume of distribution

kel = population elimination rate

tinf = length of infusion

 

iv.  Calculate ideal dosing interval (tau)

 

tau = tinf + [-1 / kel x ln (Cptmax/Cptmin)]

where Cptmin = Target trough

Cptmax = Target peak

 

v.   User selects practical dosage and interval

 

vi.  Calculate expected steady-state peak & trough levels        

Cpssmax = [MD / (tinf x Vd x kel)] x [(1 - e-kel x tinf) / 1-e-kel x tau)]

 

Cpssmin =   Cpssmax * e-kel x (tau - tinf)

 

 

Traditional method

Adjust maintenance dose using the Sawchuk and Zaske method

 

1.  Calculate elimination rate (kel)

 

kel = (ln Cpmax/Cpmin') / time between samples        

where Cpmax = Peak level

Cpmin' = Trough level after the dose

 

2.  Calculate volume of distribution (Vd)

 

Vd = [(Dose/tinf) / kel]  x  {(1 - e-kel x  tinf) /  [Cpmax - (Cpmin x e-kel x  t')]}

where Cpmax = Peak level

Cpmin = Trough level before the dose

tinf = infusion time

t' = hours between time Cpmin drawn and end of infusion

 

3.  Calculate ideal dosing interval (tau)

 

tau = tinf + (-1/kel) x  ln (Cptmax/Cptmin)

where Cptmin = Target trough

Cptmax = Target peak

 

4.  Calculate ideal maintenance dose (IMD)

IMD = kel   x  Vd  x  Cptmax  x  [(1 - e -kel x  tau) / (1 - e -kel x  tinf)]

 

5.  User selects practical dosage and interval

 

6.  Calculate expected peak & trough levels

 

Cpssmax =  [MD / (tinf  x  Vd  kel)]  x  [(1 -  e-kel x  tinf) / (1 -  e-kel x  tau)]

 

Cpssmin =   Cpssmax * e -kel x (tau - tinf)

 

 

Traditional method

Adjust maintenance dose using the 1-compartment Bayesian algorithm

 

1.   Minimize Bayesian function

 

The Bayesian method uses population-derived pharmacokinetic parameters (ie., Vd and kel) as a starting point and then adjusts those parameters based on the serum level results taking into consideration the variability of the population-derived parameters and the variability of the drug assay procedure. To achieve that end, the least squares method based on the Bayesian algorithm estimates the parameters kel & Vd which minimize the following function:

 

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2.  Calculate ideal dosing interval (tau)

 Same as the Sawchuk and Zaske method

 

3.  Calculate ideal maintenance dose (IMD)

 Same as the Sawchuk and Zaske method

 

4.  User selects practical dosage and interval

 

5.  Calculate expected peak & trough levels

 Same as the Sawchuk and Zaske method

 

 

Extended interval method

Initial dose

 

1.  Calculate dosing weight (DW)

 Same as Sawchuk and Zaske's method

 

2.  Calculate maintenance dose (MD)

 MD = DW x QDdose

         where QDdose is the daily dose in mg/kg:

Amikacin, kanamycin   = 15 mg/kg

Gentamicin, Tobramycin, Netilmicin = 5 mg/kg

 

3.  Determine interval

 Interval is based on creatinine clearance        

CrCl

Interval

Over 60

24 hours

40 - 59

36 hours

30 - 39

48 hours

Less than 30        

Use traditional methods

         

 

Extended interval method

Adjust maintenance dose

 

1.  Determine interval

Obtain a mid-interval drug level 6 to 16 hours after the initial dose, then evaluate the interval based on the dosage adjustment nomogram.

 

If the 6 to 16 hour level is undetectable and the infection is not responding, consider changing to a traditional dosing method.

 

The three interval break points on the graphs are decay curves, produced by using a population average volume of distribution of 0.25 L/kg and an elimination rate calculated from creatinine clearances of 25, 40, and 60 ml/min for 48, 36, and 24 hour intervals respectively. The authors of the Hartford nomogram then flattened these decay curves to simplify the nomogram. The Hartford nomogram is utilized by Kinetics if your model EI dose is 7mg/kg.

 

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It is important to note that the Hartford ODA nomogram is only valid for a 7mg/kg dose.  An interval adjustment nomogram for the less aggressive dose of 5mg/kg/day was developed by a consensus panel. For 15mg/kg doses of amikacin multiply the drug-level scale by a factor of three. The consensus nomogram is utilized by Kinetics if your model EI dose is 5mg/kg.

 

 

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This same consensus panel argues that the 48 hour interval should be abandoned, that patients with a CrCl <  40ml/min should be dosed by traditional pharmacokinetic methods..

 

Furthermore, some have questioned the validity of all ODA nomograms because they are based on one-compartment parameters derived from studies of traditional dosing methods.  Some pk studies have shown that the pharmacokinetics of aminoglycosides at high doses differ significantly from those at traditional doses.  Therefore, it is argued that nomograms based on an assumption of similar kinetics are invalid.

 


See also:

Introduction

Monitoring parameters

Precautions

Bibliography

 

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