Pharmacokinetic Dosing Review (2012)

(Murphy JE – Clinical Pharmacokinetics)

Key statements :

Aminoglycosides:

1. Adult Vd – range: 0.3 +/- 0.13 L/kg
2. Use adjusted body weight if actual body weight is >20% over IBW.
3. Emaciated patient (ABW/IBW ≤0.75):  Dosing weight = ABW x 1.13
4. Volume of distribution for all patients except for emaciated, severely ill and trauma patients:
   0.3 L/kg.  Emaciated patients: Vd=0.35 L/kg.    Severely ill/trauma pts:  0.4 L/kg.
5. Estimating clearance:
   Method 1:  CL_ag = CrCl.  CrCl (L/hr) = CrCl (ml/min) x 0.06.  Kel =  CL_ag/Vd
   Method 2: Kel = (0.0024 x CrCl) + 0.01

Key statements:

Vancomycin:

1. Adult Vd (≥16 – <65 years old): 0.62 +/- 0.15 L/kg
2. Kel = 0.00083(CrCl) + 0.0044     – CrCl is in ml/min.

(Winter ME – Basic Clinical Pharmacokinetics)

Key statements :

Aminoglycosides (pp 134 – 181):

1. Vd: 0.25 L/kg (must adjust for obesity or changes in extracellular fluid status.)
2. Vd (obese patients): (0.25 L/kg)(IBW) + 0.1(TBW – IBW)
3. Kel =  CL/Vd.     CL=CrCl (L/hr) = CrCl (ml/min) x 0.06.

Vancomycin (pp 459 – 487):

1. Vd – average: 0.7 L/kg TBW   or    
   Vd  in adults (≥18 years old) = 0.17(age in years) + 0.22(TBW) + 15
2. Vancomycin Cl = ~CrCl (ml/min)
3. Vanco CL (L/hr) =CrCl (L/hr) = CrCl (ml/min) x 0.06.
4. Kel =  Vanco CL/Vd.

(Burton ME et al.   Applied Pharmacokinetics & Pharmacodynamics )

Key statements :
Vancomycin (pg 337 – table 15-5):

(Dipiro JT et al.  Concepts in Clinical Pharmacokinetics )

Key statements :

Aminoglycosides (pp 159 – 178):

1. Commonly used regression equation for Kel = 0.00293(CrCl) + 0.014
2. Vd = 0.24 L/kg (IBW)

Vancomycin (pp 179 – 193):

1. Vd – May vary widely, however, commonly used average Vd = 0.9 L/kg total body weight
2. K_e = 0.00083(CL_{cr – ml/min}) + 0.0044  (based on population estimates – regression analysis)

(Bauer LA  – Applied Clinical Pharmacokinetics )

Key statements :

Aminoglycosides:

1. Adult, normal renal: Volume of distribution (Vd): 0.26 L/kg (range: 0.2-0.3 L/kg)
   Obesity (>30% over IBW) with normal renal function: Vd (in L) = 0.26 [IBW + 0.4(TBW – IBW)]
2. ELIMINATION RATE CONSTANT ESTIMATE:   Ke= 0.00293(CrCl) + 0.014
3. CrCl calculation in obese patients:   Use Salazar-Cocoran method if weight >30% above IBW.
   For Men:
   [137 – age] x [(0.285 x weight(kg)) + (12.1 x height(m)²)]
   ———————————————————–
   (51 x SCr)For Women:
   [146 – age] x [(0.287 x weight(kg)) + (9.74 x height(m)²)]
   ———————————————————
   (60 x SCr)

Vancomycin:

1. Vd – 0.7 L/kg (most patients)
2. Vanco Cl (in mL/min/kg) = 0.695(CrCl in mL/min/kg) + 0.05″Because each clearance value is normalized for the patient’s weight, the estimated or measured creatinine clearance must be divided by the patient’s weight in kilogram before using it in the equation, and the resulting vancomycin clearance must be multiplied by the patient’s weight if the answer is needed in the units of mL/min. The weight factor that is used for all individuals, including obese patients, is total body weight (TBW)”

   ke = Vanco Cl/V
   Ke (hr^-1) = [(0.695[(CrCl mL/min)/TBW kg] + 0.05)  x 0.06] / 0.7 ]

3. CrCl calculation in obese patients:   Use Salazar-Cocoran method if weight >30% above IBW.
   For Men:
   [137 – age] x [(0.285 x weight(kg)) + (12.1 x height(m)²)]
   ———————————————————–
   (51 x SCr)For Women:
   [146 – age] x [(0.287 x weight(kg)) + (9.74 x height(m)²)]
   ———————————————————
   (60 x SCr)

References

1. Bauer LA. The Aminoglycoside Antibiotics. In Bauer LA, ed. Applied Clinical Pharmacokinetics. 2nd ed. New York, NY: McGraw Hill Medical; 2008:97-206.
2. Bauer LA. Vancomycin. In Bauer LA, ed. Applied Clinical Pharmacokinetics. 2nd ed. New York, NY: McGraw Hill Medical; 2008:207-298.
3. Burton ME, Shaw LM, Schentag JJ, Evans WE. Applied Pharmacokinetics & Pharmacodynamics: Principles of Therapeutic Drug Monitoring. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2006.
4. DiPiro JT, Spruill WJ, Wade WE, Blouin RA, Pruemer JM. Concepts in Clinical Pharmacokinetics, (5th Edition) 2010. American Society of Health Systems Pharmacist, Bethesda, MD.
5. Murphy JE. Aminoglycosides. In: Murphy JE, ed. Clinical Pharmacokinetics, 4th ed. Bethesda, MD: American Society of Health-System Pharmacists, 2008:27-60.
6. Winter ME. Basic clinical pharmacokinetics. 5th ed. Baltimore: Lippincott Williams and Wilkins; 2010.
7. Winter MA, Guhr KN, Berg GM. Impact of various body weights and serum creatinine concentrations on the bias and accuracy of the Cockcroft-Gault equation. Pharmacotherapy 2012; 32: 604-612 [PMID: 22576791 DOI: 10.1002/j.1875-9114.2012.01098.x]
   

   Quotes: [Largest study so far….total of 3678 patients] Regarding Salazar equation: This equation, however, was not consistently shown in studies to be a superior predictor of renal function. It is not widely used in clinical practice and has not been validated in pharmacokinetic studies. In addition, the Salazar-Corcoran equation is not recognized by the National Kidney Foundation.Regarding CG -LBW equation: Our findings do not support those conclusions and are different from a recent investigation of Clcr in 54 morbidly obese patients that found that adjusting an obese patient’s weight to a fat-free weight or lean body weight predicted a Clcr calculated with the C-G equation without bias. Notably, our study included 2065 obese or morbidly obese patients, far more than other published studies.  Conclusions: An unbiased C-G Clcr can be calculated using actual body weight in underweight patients and ideal body weight in patients of normal weight. Using ABW0.4 for overweight, obese, and morbidly obese patients appears to be the least biased and most accurate method for calculating their C-G Clcr. Rounding Scr in patients with low Scr did not improve accuracy or bias of the Clcr calculations.

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