| Section 2 - Applied Pharmacokinetics |
Choosing a model
The 2-compartment vancomycin model utilized by Kinetics is based on Lake and Peterson's data and is meant to approximate their published nomogram. L&P's method, which is the only published vancomycin dosing method to be independently verified, achieves target peaks of 20 to 30 mcg/ml and target troughs of 5 to 10 mcg/ml in 80% of patients.
Initial dosing
Kel = 0.009 + (CL_{cr} x 0.0022)
where
Vd = DW x Vd_{perkg}
where
tau = t_{inf} + [ln(Cp_{tmax} / Cp_{tmin}) / Kel]
where
MD = Kel x Vd x Cp_{tmax} x (1 - e^{-Kel x tau} / 1 - e^{-Kel x tinf})
where
CL = [0.17 + (CL_{cr} x 0.06)] x (DW / 70)
where
Creatinine Clearance | Dosing interval |
>90 | 6 hours |
70-89 | 8 hours |
46-69 | 12 hours |
30-45 | 16 hours |
15-29 | 24 hours |
tau = 6 x (72 / [(10 * CL) + 1.9])
k_{0} = 1/{[(k_{12}-k_{d}) (1 - e^{kd x tinf}) e^{kd x t})] / [V_{c} x k_{d} (k_{d}-k_{el}) (1 - e^{kd x tau})] +
[(k_{el}-k_{21}) (1 - e^{kel x tinf}) e^{kel x t})] / [V_{c} x k_{el} (k_{d}-k_{el}) (1 - e^{kel x tau})]} / 1/CP_{target}
where
1-compartment serum level analysis
Bayesian analysis
The Bayesian method uses population-derived pharmacokinetic parameters, Vd and CL, 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.
The appeal of this approach is that it mimics human thinking. That is, SDC's are interpreted in light of both our expectations from the population model and our knowledge of the variability of the test itself.
The main advantage of Bayesian analysis is that only one steady-state SDC, preferably a trough, is required to perform an accurate analysis.
| Section 2 - Applied Pharmacokinetics |