kinetics

Aminoglycoside-Vancomycin Dosing
Patient Name: Location:  
 Select drug:     - Program Hints - 
Need dosing information for once daily dosing? 
Age:      Weight:      Gender: 
SCR:     Height:
Desired peak:    Desired trough:  Infusion time: hours
Volume of distribution:   L/kg
Usual range: aminoglycosides: 0.25-0.35
Vancomycin: 0.65 - 0.9
 
Note: original version before the latest update is located here.

Program Hints
Selecting the infusion time
 
Infusion time (ti)
Sample recommendations
Aminoglycosides:   (All doses) 0.5
Vancomycin   
(0 - 500mg/  0.5 )		 0.5
501 - 1250 mg 1
1251 -1750 mg 1.5
1751 - 2250 mg 2
Sample recommendations for peak / trough concentrations

(Review levels) Gentamicin /
           Tobramycin 		Amikacin Vancomycin
Infection Site Peak Trough Peak Trough Peak Trough
Abdominal 6-7 <1 25-30 4-6    
Cystitis 4-5 <1 20-25 4-6    
Endocarditis 4-12 <1.5 25-30 <8 30-40 5-15
Osteomyelitis 6-7 <1 25-30 4-6 30-40 5-20
Pneumonia 8-10 <1.5 25-30 <8 30-40 5-20
Pyelonephritis 6-7 <1 25-30 4-6 25-35 5-10
Sepsis 7-8 <1 25-30 4-6 25-35 5-15
Soft tissue 6-7 <1 20-25 <6 25-35 5-10
Synergy 5-6 <1 20-25 4-6 25-35 5-10
Wound Infections 6-7 <1 25-30 <6 25-35 5-10
Vancomycin - Target trough levels??
M. Goodwin, E. Ashley. Vancomycin: can we teach the mainstay of therapy for gram-positives new tricks?   Special to Infectious Disease News. February 2006.
http://www.infectiousdiseasenews.com/200602/frameset.asp?article=pharmconsult.asp
Accessed: December 15th, 2006
"Independent of the reason, many clinicians are now targeting higher troughs for vancomycin (from 15 to 20 µg/mL), especially when treating more deep-seated infections (ie, meningitis, endocarditis, osteomyelitis), in which vancomycin penetration may also be an issue."
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"The recent pneumonia guidelines, a joint publication from the American Thoracic Society and the Infectious Diseases Society of America (IDSA), advocate targeting higher vancomycin trough concentrations. Vancomycin is a large molecule, and we have known for sometime that penetration into the lung and other infection sites may be difficult. Therefore, increasing the target trough serum concentrations may result in higher pulmonary drug concentrations.  The recommended target vancomycin trough in these guidelines is 15 to 20 µg/mL. However, there are no specific data to say that troughs more than 15 µg/mL are associated with improved outcomes over trough levels more than 5 or 10 µg/mL."   
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"Because many clinicians consider the vegetations involved in endocarditis to be relatively difficult to penetrate, the traditional target troughs were 15 to 20 µg/mL for this infection. The recent guidelines, however, recommend a lower trough concentration of 10 to 15 µg/mL. As with the pneumonia guidelines, these targets reflect the opinion of the expert panel in the absence of data to document the ideal target."
See link above for the complete article....

L. Briceland. Ask the Experts about Pharmacotherapy - From Medscape Pharmacists. Would You Explain the Current Recommendations for Vancomycin Trough Levels? 
http://www.medscape.com/viewarticle/508120    Accessed: December 15th, 2006
"More recently, recommendations for optimal therapeutic serum concentrations have varied widely: none at all except in select clinical situations[3]; 5-10mcg/mL[2]; 5-15 mcg/mL[4]; and 5-20 mcg/mL.[5] These recommendations have arisen specifically due to the lack of clear evidence for the concentrations needed to maintain therapeutic efficacy and avoid concentration-dependent toxicity[6] and the understanding that vancomycin exerts concentration-independent killing." "Exceeding the minimum inhibitory concentration (MIC) by 4-5 times does not produce further cidality; thus, the ranges cited would provide adequate serum and tissue concentrations to kill most pathogens (in which the MIC is generally less than 2 mcg/mL).[5] The current dosing regimen of 15 mg/kg every 12 hours (in normal renal function) is still employed with the intent of achieving therapeutic troughs (now broadly defined as anywhere between 5-20 mcg/mL)."     See link above for the complete article....
Background information

Background information  (Equations listed are calculated by the program)
Obtain baseline data:
Patient age, sex, height, weight, allergies, diagnosis, infection site, current 
drug therapy, I/O's for past 24 hours, Tmax, WBC with diff, albumin, 
Past medical history, Lab work-up: Scr, Bun, cultures etc.
Estimate Ideal body weight in (kg)
 Males: IBW = 50 kg + 2.3 kg for each inch over 5 feet.
 Females: IBW = 45.5 kg + 2.3 kg for each inch over 5 feet.
If the actual body weight is greater than 25% of the calculated IBW, calculate the adjusted body weight (ABW):            
 ABW = IBW + 0.4(Total body weight - IBW) 
Estimate Creatinine Clearance: (ml/min)
       Cockcroft and Gault equation:
       CrCl = [(140 - age) x IBW] / (Scr x 72)       (x 0.85 for females)
       Note: if the ABW (actual body weight) is less than the IBW use the 
       actual body weight for calculating the CRCL. If the patient is >65yo and 
       creatinine<1,  use 1 to calculate the creatinine clearance
Estimate kel (Elimination rate constant):
  Amikacin /Gentamicin/Tobramycin: Kel = (0.00285 x CrCl) + 0.015
      May also use: (0.003 x CrCl) + 0.01
  Vancomycin: kel = (0.00083 x CRCL)  + 0.0044 (used by program)
        Equation used by the Detroit VA Medical Center: CRCL x 0.0012

     The above equations provide an estimate of the elimination rate
     constant based on population kinetics. The following may decrease
     the usefulness of these equations:
          *Renal failure, CHF, Burn patients, cystic fibrosis, severe
            hypotension, rapidly changing renal function. (Burn victims 
            and patients with cystic fibrosis usually have increased 
            rates of elimination. Patients with CHF or severe hypotension 
            will have decreased rates of elimination due to decreased 
            renal perfusion).
Estimate half-life (T1/2) in hours:
      T1/2 = 0.693 / Kel
Estimate Volume of Distribution (Vd): (Liters)
Aminoglycosides:
    Use IBW unless obese, then use ABW= 0.4 x (TBW-IBW) + IBW
    Vd (Normal) = 0.25 to 0.3 L/kg Vancomycin:
    [Use actual body weight unless obese (> 30% over IBW)-then use adjusted 
    body weight  = 0.4(TBW- IBW) + IBW.]
    Vd (Normal): 0.6 to 0.7 L/kg 
Select Time of Infusion (ti):
(a) Aminoglycosides: 30 minutes (0.5 hrs)
(b) Vancomycin: 0-500 mg/ 0.5 hrs ; 501 to 1250 mg/ 1 hour ;
        1251 to 1750/ 1.5 hrs ; >1750/ 2 hours
Calculate Dosing Interval (T)    hrs.
    T = Ln (Cmax/Cmin) / kel + ti or estimated T = 3 x T1/2
Calculate Maintenance dose (MD):_____mg.
   MD = [(kel) x (Vd) x (ti) x (Cpeak desired) x (1 - e-kT)] / (1 - e-kti)
     or MD = (Cpeak desired) x Vd (eg: C = D/V, therefore D=C*V)
Calculate Predicted Peak and Trough at Steady State.
          Cmax = [Dose * 1-e-kti] / (kel)(Vd)(ti) 1-e-kT

          Cmin = Cmax * e-k(T-ti)
 

References
1) Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16(1):31-41

2) Davis GA, Chandler MH. Comparison of creatinine clearance estimation methods in patients with trauma. Am J Health-Syst Pharm 1996;53:1028-32.

3) Dawson-Saunders B, Trapp RG. Basic and Clinical Biostatistics. 2nd ed. Norwalk, CT: Appleton & Lange; 1994.

4) Dettli LC. Drug dosage in patients with renal disease. Clin Pharmacol Ther 1974;16:274-80.

5) Drusano LG, Munice HL, Hoopes JM et al. Commonly used methods of estimating creatinine clearance are inadequate for elderly debilitated nursing home patients. J Am Geriatrics Soc 1998;36:437-41.

6) Hailemeskel B, Namanny M, Kurz A. Estimating aminoglycoside dosage requirements in patients with low serum creatinine concentrations. Am J Health-Syst Pharm 1997;54:986-7.

7) Jelliffe RW. Estimation of creatinine clearance when urine cannot be collected. Lancet 1971;1:975-6.

8) Levey AS, Greene T, Kusek JW, et al. A simplified equation to predict glomerular filtration rate from serum creatinine (Abstr) J Am Soc Nephrol 2000;(11):155A

9) Levey AS, Greene T, Schluchter MD, et al. Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group. J Am Soc Nephrol 1993;4(5):1159-71

10) Levey AS. Assessing the effectiveness of therapy to prevent the progression of renal disease. Am J Kidney Dis 1993;22(1):207-14

11) Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130(6):461-70

12) Rhodes RS, Sims PJ, Culbertson VL et al. Accuracy of creatinine clearance estimates in geriatric males with elevated serum creatinine clearance. J Geriatric Drug Ther 1991;5:31-45.

13) Smythe M, Hoffman J, Kizy K et al. Estimating creatinine clearance in elderly patients with low serum creatinine concentrations. Am J Hosp Pharm 1994;51:189-204.