| 1. A 20 year old, 5'5" female weighing 60kg is started on cefoxitin 1 g q6h and gentamicin for the treatment of pelvic inflammatory disease. Her physician would like your recommendation on an initial gentamicin dose and interval for this patient. SCr = 1.0 mg/dL, WBC = 15,000/mm3, Temp = 101°F a. Calculate her lean body weight LBW = 45 + 2.3(5) = 56.5 kg b. Calculate her creatinine clearance: CrCl = [((140-20) x 56.5) / (72 x 1.0)] x 0.85 = 80 mL/min c. Calculate an estimated gentamicin half-life: kd = 0.0024(80) + 0.01/h = 0.202 h-1
t1/2 = 0.693/0.202 = 3.43 h d. Calculate an appropriate initial dosage interval: T = (2 to 3) x 3.43 = 6.86 to 10.29 h
T = 8 h e. Calculate an appropriate initial gentamicin dose: D = (1.5 - 2.5) x (56.5) = 85 mg - 141 mg
round to nearest 5 mg increment f. Please recommend exact times to draw levels after the first dose, which is scheduled to be administered at 1400 and will be infused over 1 hour: 1.5 x t1/2 = 1.5 x 3.43 h = 5 h; spaceover at least 5 h
1st level: 15-30 min post, 1515 - 1530
2nd level: 3 h post, 1800
3rd level: 5-6 h post, 2000-2100 2. R.B. is a 35 year old male admitted s/p a GTC seizure with symptoms of aspiration pneumonia. Clindamycin 900mg q8h and gentamicin 200mg q8h were ordered by the physician during the night. You are consulted in the morning after the first dose of gentamicin has been administered and the second dose is scheduled to be infused over 1 hour starting at 1100.
Ht: 5'11", Wt: 100Kg, BUN: 15 mg/dL, SCr: 1.2 mg/dL a. Calculate his lean body weight LBW = 50 + 2.3(11) = 75.3 kg
DW = (100-75.3)0.4 + 75.3 = 85 kg b. Calculate his creatinine clearance: CrCl = [((140-35) x 75.3) / (72 x 1.2)] = 91.5 mL/min c. Calculate the elimination rate constant: kd = 0.0024(91.5) + 0.01 = 0.2296 h-1 or 0.23 h-1 d. Calculate the estimated gentamicin half-life: t1/2 = 0.693/0.23 = 3 h e. Make a recommendation on when to draw levels: (i.e., around which dose, and at what times) Order 3 levels around the 2nd dose as the patient's condition is critical. Draw
a trough at 1045, and 2 post infusion levels at 1230 and 1700. The patient is not
at steady-state, therefore peak/trough kinetics are inappropriate. Gentamicin levels were performed with the following results: 1045 - 2.4 mg/L 1100-1200 - 200mg gentamicin infused 1230 - 9.4 mg/L 1700 - 3.0 mg/L Graph the above levels and use the graph to answer the following questions f. Using the best data available, calculate his elimination rate constant: From graph: kd = 1n 9.4 - 1n3 = 0.25 h-1
5 - 0.5 g. Determine his extrapolated peak: From graph: 10.5 mg/L (@ 1200) h. Determine his extrapolated trough: C2 = C1e -kt = 2.4e -0.25(0.25) = 2.3 mg/L (@1100) (remember: kd should not change) i. Calculate RB's volume of distribution: Vd = [(200/1)/0.25] x [(1-e-(0.25 x 1)/10.5 - (2.3 e-(0.25 x 1))]
Vd = 20.3 L
or 20.3 L/75.3 kg = 0.27 L/kg j. Determine an appropriate dosing regimen (dose and interval) for R.B.: T = (-1/0.25) (ln 1/8) + 1
T = 9.32 h --> 8 h Ko = (0.25)(20.3)(8) [(1-e -0.25 x 8) / (1-e -0.25 x 1)]
ko = 158.1 mg/h --> 160mg 160 mg q 8 h k. Calculate the peak and trough you expect to achieve on the new regimen: Cpmax = [(160)(1 - e -0.25 x 1)] / [(0.25)(20.3)(1-e -0.25 x 8)]
Cpmax = 8.11 mg/L Cpmin = (8.11)(e -0.25(8-1))
Cpmin = 1.41 mg/L 3. BH is a 55 year old woman receiving clindamycin 900mg IV q8h and gentamicin 100mg IV q 12 h for the treatment of a diabetic foot ulcer. SCr = 1.0 mg/dL, WBC = 12,000/mm3, Temp = 101°F, Weight = 65 kg, Height = 5'2". A pharmacokinetic study is performed at steady-state around her 0900 dose. 0845 - 1.2 mg/L
0900-0930 - gentamicin infused
1000 - 9.0 mg/L a. Using the best information available, determine the patient's half-life: kd = 0.1874 h-1 t1/2 = 3.7 h 1n 9 - ln 1.2 11.25 - 0.5 b. Determine the extrapolated peak concentration: from graph: 10 mg/L (@ 0930) c. Determine the extrapolated trough concentration: Cmin = 1.2 e -0.1874 (0.25) = 1.15 mg/L (@ 0900)
(Remember: since we're at steady-state, the trough @ 0900 should be the
same as the trough (@ 2100) d. Determine the volume of distribution: Vd = [(100/0.5) / 0.1874] x [(1-e -(0.1874 x 0.5) / 10 - (1.15 e-(0.1874 x 0.5)]
Vd = 10.7 L
or 10.7 L/49.6 kg = 0.22 L/kg e. Please recommend an appropriate gentamicin dose and interval that would result in peaks of 6-7 mg/L and a trough of less than 1.0 mg/L T = (-1/0.1874) (1n 1/7) + 0.5
T = 10.9 h --> 12 h Ko = (0.1874)(10.7)(7) [(1-e -0.1874 x 12) / (1 -e -0.1874 x 0.5)]
Ko = 140 mg/h --> Dose = 140mg 0.5h = 70mg 70 mg q 12 h f. Calculate the peak and trough you expect to achieve on the new regimen Cpmax = [(140)(1 - e -0.1874 x 0.5)]/[(0.1874)(10.7)(1-e -0.1874 x 12)]
Cpmax = 6.98 --> 7 mg/L Cpmin = (7)(e -0.1874(12 - 0.5))
Cpmin = 0.812 mg/L 4. A 28 year old, 70kg male with normal renal function is being treated with tobramycin 140mg IV loading dose and piperacillin 3g IV q4h for Pseudomonas aeruginosa bacteremia. A pharmacokinetic study is performed on the first dose and the following results are obtained: 1000-1100 - infusion of tobramycin
1130 - 2.5 mg/L
1330 - 1.2 mg/L
1500 - 0.7 mg/L a. Graph the data and determine the patient's half-life: Using slope: kd = 0.371h-1 t1/2 = 1.87 h 1n 2.1 - 1n1 = 0.371h-1
3 - 1 b. Determine the extrapolated peak and trough concentrations: Cpmax = 3.0 mg/L (@1100)
Cpmin = 0 for first dose (@1920) c. Calculate the patient's volume of distribution: Vd = [(140mg/l h) / (0.371)][1-e -0.371 x 1) / (3)
Vd = 39 L
or 39 L/70 kg = 0.56 L/kg d. Explain the results of the study: Vd is too large, normal is 0.25 L/kg
large Vd from fluid excess, draining surgical wound, leaking IV bag,
dose not completely infused, inactivation by piperacillin 5. KK is a 32 year old male receiving gentamicin 100mg IV q8 hours. The pharmacokinetic study was performed around his first dose and the results are as follows: 1200-1300 - first dose infused
1330 - 5.0 mg/L
1600 - 1.25 mg/L
1830 - 2.5 mg/L a. Explain the results of this study: The 1600 and 1830 levels are switched b. Graph the data and determine the half-life: Using slope: kd = 0.28 h-1 t1/2 = 2.5 h 1n 4.4 - 1n 1.9 = 0.28 h -1
4 - 1 c. Determine the extrapolated peak: From graph: 5.7 mg/L (@1300) | 
