Vancomycin models

Vancomycin pharmacokinetics vary widely between patients. Compared to aminoglycosides, vancomycin exhibits a much broader range of values within the normal distribution, reflective of a large standard deviation. This is illustrated by comparing distribution curves for Vd:

Figure 1. Comparative Vd Distribution of Aminoglycosides and Vancomycin
bell curve

The following table summarizes several vancomycin 1-compartment models, collected from the published literature and from colleagues. The table illustrates the large differences in published vancomycin model parameters. This comparison emphasizes that vancomycin pharmacokinetic parameters vary widely between studies. One can logically conclude that a single vancomycin model cannot be applied to all patient populations.

Table 1. Vancomycin Model Parameters
Source Elimination rate/Clearance Volume of distribution
Ambrose CL ml/min = CrCl (0.17 × [age in years]) + (0.22 × [ABW in kg]) + 15
Bauer CL ml/min/kg = 0.05 + (CrClml/min/kg x 0.695) 0.47 L/kg
Birt Kel = 0.0726 + (CrCl x 0.000545) 0.54 L/kg
Burton CL ml/min = 0.04 + (CrCl x 0.0075) 0.47 L/kg
Burton revised CL L/hr = CrCl x 0.048 0.706 L/kg
Matzke CL ml/min = 3.66 + (CrCl x 0.689) 0.72 L/kg if CLcr is >60 mL/min
0.89 L/kg if CLcr is 10–60 mL/min
0.90 L/kg if CLcr is <10 mL/min.
Matzke variation Kel = 0.009 + (CrCl x 0.0022) 0.90 L/kg
Moellering Kel = 0.074 + [CrClml/min/kg x 0.08] 0.90 L/kg
Rodvold CL ml/min = 15.7 + (CrCl x 0.79) 0.50 L/kg if CLcr is >70 mL/min/70 kg
0.59 L/kg if CLcr is 40–70 mL/min/70 kg
0.64 L/kg if CLcr is 10–39 mL/min/70 kg
Abbott CL L/hr = 0.05 + (CrCl x 0.75) 0.65 L/kg
Creighton Kel = 0.0044 + (CrCl x 0.00083) 0.70 L/kg
VA CL ml/min = CrCl x 0.9 0.70 L/kg
Winter CL L/hr = CrCl x 0.65 0.70 L/kg

Most of these models are described in their respective articles as "accurate" (p < 0.01). But how can that be? The dissimilar model parameters seem contradictory. The diversity is due, in part, to the disparate patient populations studied. Some have studied a general med/surg population, others elderly veterans, while others describe an ICU population.

Vancomycin dosing methods

Below is a table summarizing the most popular vancomycin dosing methods. Stating the obvious, even the experts can't agree on a single dosing strategy for all patients.

Table 2. Vancomycin Dosing Methods
Source Dose Interval
Package insert 500mg Q 6 hrs
1g Q 12 hrs
Lake & Peterson 8 mg/kg
CrCl Interval
90 and above 6 hrs
70 to 89 8 hrs
46 to 69 12 hrs
30 to 45 16 hrs
15 to 29 24 hrs
Matzke LD = 25 mg/kg
MD = 19 mg/kg 		See Figure 1 below
Moellering See Figure 2 below See Figure 2 below
Nielson LD = 25 mg/kg
MD = [(15 x CrCl) + 150] mg/day 		Not specified
Rotschafer 6.5-8 mg/kg Q 6-12 hrs

Figure 2. Matzke Vancomycin Dosing
Matzke

Figure 3. Moellering Vancomycin Dosing
Moellering

Conclusion

A logical conclusion from this conflicting data is, use the model that's best for your patient population. Don't rely on someone else's model to dose your patients. If you treat a diverse patient population, you may need multiple vancomycin models. This is where the population analysis utility included with Kinetics© and APK© will allow you to create models fitted to your patient population.

Population models of vancomycin can not be relied upon to accurate predict individual patient pk parameters. Vancomycin has both a highly variable Vd and an unpredictable Nonrenal clearance component. Therefore, initial pharmacokinetic predictions should be viewed as rough estimates of dosage requirements. Experienced clinicians suggest a weight-based nomogram for estimating initial dosage needs, with subsequent pharmacokinetic analysis of serum level data, as the best common sense strategy for dosing vancomycin.

Click here to read an interesting vancomycin case.

Epilogue

An evaluation of the accuracy of seven popular vancomycin dosing methods has recently been published. John Murphy and colleagues concluded "The seven methods studied for estimating vancomycin pharmacokinetic parameters varied widely in predicting vancomycin trough concentrations compared with measured serum concentrations and were not sufficiently reliable to replace therapeutic monitoring of vancomycin serum concentrations."21

Predictability of Vancomycin Trough Concentrations Using Seven Approaches for Estimating Pharmacokinetic Parameters

References

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