PK Module 14: In-Class Activity 1

Estimate the vancomycin clearance (in L/hr) for a 60-year-old patient who weighs 70 kg and has a creatinine clearance 75 mL/min. Round to the nearest hundredth.

Cl_Vanc (L/hr)= [0.69*(CrCl) + 3.66] x 0.06

(a)  

Answer explanation

Cl_Vanc (L/hr)= [0.69*(CrCl) + 3.66] x 0.06

Cl_Vanc (L/hr)= [0.69*(75) + 3.66] x 0.06

Cl_Vanc (L/hr)= 3.32

After administration of the loading dose and seven doses (1500 mg each) at 12-hour intervals, plasma vancomycin concentrations are determined to be 44 mg/L (2 hours after the end of the 2-hour infusion) and 16 mg/L at the end of the dosing interval. 

What is the half-life of vancomycin (in hr) in this patient?

(a)  

Answer explanation

Ke = ln (C1/C2)/t2-t1

K = ln (44mg/L/16mg/L) / (12 - 4 hr) = 0.126 hr-1

t1/2 = 0.693/K = 0.693/0.126 = 5.5 hr

Calculate the Ke (in hr-1) for a patient that will be initiated on vancomycin using the equation Ke = 0.00083/hr x CrCl + 0.0044 for a 45-year-old man, 5' 10'' tall, weighing 73 kg (IBW = 73 kg), serum creatinine concentration of 1.00 mg/dL.

Ke = 0.00083/hr x CrCl + 0.0044 

(a)  

Answer explanation

Step 1: Calculate CrCl

CrCl = (140-45)(73)/(72 x 1) = 96.3 mL/min

Step 2: Calculate Ke

Ke = 0.00083/hr x CrCl + 0.0044 = 0.00083/hr(96.3) + 0.0044 = 0.084 hr-1

BW, a 42-year-old man, 5' 10'' tall, weighing 75 kg (IBW = 73 kg), needs to receive a loading dose of vancomycin (25 mg/kg) that will be infused over 2 hours.  

Calculate the loading dose for this patient in mg. For grading purposes do not round.

(a)  

Answer explanation

LD = 25 mg/kg x 75 kg = 1875 mg

A patient is receiving 750 mg of vancomycin every 12 hours by 1-hour infusion. A steady state trough concentration is measured  0.5 hours before a dose and reported as  12 mg/L. You wish to raise the trough to  17.5 mg/L. 

What dose (rounded to nearest mg) would you suggest if the interval would remain at 12 hours?

(a)  

Answer explanation

Set up a ratio

Dose1/Conc1 = Dose 2/Conc2

750/12 = Dose2/17.5

Dose = 1094 mg

A patient is receiving 750 mg of vancomycin every 12 hours by 1-hour infusion. A steady state trough concentration is measured  0.5 hours before a dose and reported as  12 mg/L. You wish to raise the trough to  17.5 mg/L. 

What dosing interval should you use if you wish to keep the dose at 750 mg? Do not round

(a)  

Answer explanation

Taunew = (Css old)/(Css new) x Tau old

Taunew = (12/17.5) x 12 hr

Taunew = 8.2 hours Round to 8 hours

E.K., a 60-year-old, 50-kg woman with a serum creatinine of 1.0 mg/dL, has been empirically started on 750 mg of vancomycin every 12 hours. A culture indicates that the infection is caused by MRSA with an MIC of 1.0 mg/L. Design a dose in mg to be administered every 24 hr that will produce therapeutic vancomycin concentrations and an AUC₂₄/MIC ≥ 400 for E.K. You have calculated her patient specific K = 0.054 hr-1 and V_d = 34.8 L.

       AUC₂₄/MIC = X₂₄ / (Cl x MIC)

(a)  

Answer explanation

Step 1: Calculate Cl

Cl = V x K = 34.8 L x 0.054 hr-1 = 1.88 L/hr

Step 2: Calculate Dose

Dose_24hr = AUC₂₄/MIC x Cl x MIC

Dose_24hr = 400 x 1.88 x 1 = 752 mg

DJ is a 56-year-old, 76-kg (height = 6 ft 1 in) male with MRSA pneumonia (MIC = 1 μg/mL). His current serum creatinine is stable at 1.5 mg/dL. A vancomycin dose of 1000 mg every 24 hours was prescribed. After the third dose, the steady-state trough concentration equaled 7 μg/mL. Based on this you calculate the patient's AUC₂₄/MIC = 265. Compute a new vancomycin dose in mg that would provide an AUC₂₄/MIC > 400

(a)  

Answer explanation

Dose_new/AUC₂₄/MIC_new = Dose_old/AUC₂₄/MIC_old 

Dose_new = (1000/265) x 400 = 1509 mg/day 

RI is a 55-year-old, 78-kg (height = 6 ft 1 in) male with an MRSA pneumonia (MIC = 1μg/mL). A vancomycin dose of 1000 mg every 12 hours was prescribed and expected to achieve an AUC₂₄/MIC > 400. After the third dose, the steady-state peak and trough concentration equaled 24 μg/mL and 9 μg/mL, respectively. The dose was infused over 1 hr with a waiting period of 1/2 hour before the peak concentration was obtained. Calculate the AUC₂₄/MIC for this patient using AUC₂₄ = (AUC_inf + AUC_elim ) x # doses.

(a)  

Answer explanation

K = ln (24/9)/10.5 = 0.09 hr-1

AUC₂₄ = (AUC_inf + AUC_elim) x 2 doses (since dosed every 12 hr)

AUC₂₄ = ((((24+8)/2)*1.5)+((24-8)/0.09)) x 2 = (24 + 177.8)*2 = 403.6

AUC₂₄/MIC = 403.6/1 = 403.6

GH is a 58 yr old male (78 kg, 6'1") with MRSA. His serum creatinine is stable at 1 mg/dL. Calculate a vancomycin dosing regimen for this patient using the Rybak nomogram.

• 1250 mg every 12 hours

• 750 mg every 8 hours

• 1250 mg every 8 hours

• 1500 mg every 8 hours

• 1000 mg every 8 hours

Answer explanation

CrCl = (140-age)(wt)/72 x SCr

CrCl = (140-58)(78)/72 x 1

CrCl = 88.8 mL/min

Find on nomogram