Data Entry Creatinine Clearance/GFR Dosing/target level guidelines Pharmacokinetic parameters Dose calculation Calculate pharmacokinetic parameters Math:
Derivation of dose calculations Math:
Calculating pharmacokinetic parameters References
Data Entry
Weight: (kg) (lb) %IBW
Height: (cm) (in)
Sex: M F     Age: (yr)
Race: African/Caribbean Other
Serum creatinine: mg/dL
Derived anthropometric data
Ideal Body Weight: IBWDev
Adjusted Body Weight: ABW
Body Mass Index: BMIQuet
Body Surface Area: BSAMos
Creatinine Clearance
Cockcroft-GaultCG 62.5 ml/min
(74.3 ml/min/1.73 m²)
The Cockcroft-Gault equation is used in most vancomycin dosing situations. An alternative (e.g., Salazar-Corcoran) might be considered in patients who are obese.
JelliffeJelliffe 62.2 ml/min
Salazar-CorcoranSC 72.2 ml/min
eGFR
Original MDRD Levey(1999) 84.2 ml/min/1.73 m²
Re-expressed MDRDLevey(2006) 79.1 ml/min/1.73 m²
refit MDRD, chronic kidney diseaseRule 95.5 ml/min/1.73 m²
refit MDRD, white + healthyRule 101.9 ml/min/1.73 m²
refit MDRD, quadraticRule 110.3 ml/min/1.73 m²
WrightW 76.4 ml/min
MartinM 69.3 ml/min
CKD-EPILevey(2009) 87.4 ml/min/1.73 m²
Suggested initial dosing & target trough levels
Nosocomial pneumonia15 mg/kg q12h 15-20 mcg/ml***ATS/IDSA
Endocarditis15 mg/kg q12h 10-15 mcg/mlAdjust for trough 30-45 mcg/mlAmerican Heart Association
***12-15 mg/kg5-15 mcg/ml Dosing interval determined by CrCl:
>80: q12h;
40-79: q24h;
25-29: q48h;
<25: dose by trough level		Columbia
Line-related infection (non-MRSA)
Non-CNS Abscess, drained
Febrile neutropenia, no pathogen identified		Loading dose: 20 mg/kg
Maintenance dose: 15 mg/kg		 8-15 mcg/mlDosing interval based on CrClKingston General
MRSA
Prosthetic joint infection
Osteomyelitis
S. Aureus pneumonia
CNS infection		15-20 mcg/ml
***Loading dose: 25 mg/kg
Maintenance dose: 19 mg/kg		Peak: 30 mcg/ml
Trough: 7.5 mcg/ml		Use nomogram to adjust dose interval
(~1440/CrCl, h)		Matzke
NondialysisLoading dose: 20-25 mg/kg10-15 mcg/mlPeak: 20-30 mcg/mlPierce
Pneumonia, dialysis15-20 mcg/ml
General15 - 18 mg/kg5 - 15Initial dosing based on actual body weight:
Reduce dose by 250mg for weight over 120kg
Reduce dose by 500mg for weight over 200kg
Maximum dose 3000mg		St Luke
Concurrent aminoglycoside15 mg/kg5-10
Infected Hardware
Diabetic Foot
Osteomyelitis
Endocarditis
Pneumonia &
concurrent aminoglycoside
Severe Infections
Community acquired pneumonia		 18 mg/kg10-15
Leukemia
Pneumonia
(ventilator-associated, hospital-acquired, healthcare-associated)		20 mg/kg15-20
Vancomycin Pharmacokinetic Parameters
(using Cockcroft-Gault)
Select Kel, h -1 t1/2, h Cl, ml/min Vd, L Comments Reference
*** *** *** *** Uses Salazar-Corcoran to determine CrCl for obese patients
Uses IBW to calculate Vd in patients >130% IBW		 Bauer
*** *** *** *** - Birt
*** *** *** *** Different pharmacokinetics for patients with hematologic malignancies Buelga
*** *** *** *** Better predictor than Rushing in patients weighing within 120% IBW (Lee et al) Leonard
*** *** *** *** Loading dose of 25 mg/kg;
subsequent doses of 19 mg/kg;
dosing interval nomogram provided		 Matzke
*** *** *** ***
*** *** *** *** Loading dose 20-25 mg/kg ABW Pierce
*** *** *** *** Suggests dose (mg/kg/24h) of
0.227*CrCl (ml/min/70kg) + 5.67		 Rodvold
*** *** *** *** Better predictor than Leonard in patients
weighing > 120% IBW (Lee et al)		 Rushing
*** *** *** *** Patients with serum creatinine < 1.5 mg/dL Vance-Bryan
*** *** *** ***
Select pharmacokinetic parameters and estimate dose
Selected kel (h-1): Dosing
interval, h		68121618243648
Selected Vd (L): Dose, mg************************
Nominal infusion rate (mg/hr): Infusion
time, min		***************************
Goal Ctrough (mcg/ml): Predicted
Ctrough, mcg/ml		***************************
Predicted
Cpeak, mcg/ml		***************************
Calculate pharmacokinetic parameters from observed levels
Cpeak (mcg/ml) kel = h-1
Ctrough (mcg/ml)
Dose (mg Vd = L
Infusion time (min)
Dosing interval (hr)
Calculating dose from pharmacokinetic parameters
The differential equation determining drug concentration, C during an continuous infusion, assuming first order elimination, is given by:
where k0 = infusion rate, mass/time
Vd = volume of distribution, volume
kel = elimination constant, 1/time
 (1)Equation 1
The solution to this equation is given by:
where C0 = concentration at the beginning of the infusion		 (2)Equation 2
The differential equation determining first order elimination is: (3)Equation 3
And the corresponding solution is: (4)Equation 4
For intermittent infusion of dose D over time tinf given at time interval τ with initial concentration 0:
Substituting D/tinf for k0 in (2), define C':		 (5)Equation 5
Assume C(0) = 0. Then define C'' = C(tinf)
[at the end of 1st infusion]		 (6)Equation 6
Let τ be the dosing interval. C(τ) is then:
[just prior to 2nd infusion]		 (7)Equation 7
C(τ + tinf)
[end of 2nd infusion]		 (8)Equation 8
C(2τ)
[prior to 3d infusion]		 (9)Equation 9
C(2τ + tinf)
[end of 3d infusion]		 (10)Equation 10
C(nτ + tinf)
[end of nth infusion]		 (11)Equation 11
For sufficiently large n, the right-hand numerator term of equation (11) ≈ 0, and,
substituting for C'' from (6) and then for C' from (5), the steady state peak level is obtained:		 (12)Equation 12
And the steady state trough level is: (13)Equation 13
Vancomycin is customarily infused at a fixed rate, d', 1000 mg/1 hour.
If D/d' is substituted for tinf in equation (13), terms can be rearranged to solve for D(τ, kel, Vd, d'):		 (14)Equation 14
Equation (14) can also be solved for τ if fixed dose D is specified: (15)Equation 15
Determining pharmacokinetic parameters from drug levels
If a peak, as well as a trough level are available, pharmacokinetic parameters can be directly calculated.
From (12) and (13):		 (16)Equation 16
Solving for kel: (17)Equation 17
Substituting this kel back into (13): (18)Equation 18
References
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