Case Study 2 Answers Spring 2006

Transcription

1 Case Study 2 Answers Spring The volume of distribution of diazepam in a group of normal subjects (60 kg, ideal body weight) was found to be 105 L. In another group of patients (110 kg), the volume of distribution was found to be 305 L. Derive an equation that allows estimation of the volume of distribution based on ideal and actual body weight. Normal: IBW (60kg) 105L 1.75 L/kg Excess: EBW( = 50kg) = 200 L 4.0 L/kg (2.3 times normal) V d = 1.75 (IBW EBW)=1.75 IBW EBW

2 2. Based on the Cockcroft-Gault-Equation, calculate the amount of creatinine that is produced every hour from muscle in a normal 30 year old and 75 year old male subject (body weight 70 kg) with a serum creatinine of 1 mg/dl. The Cockroft-Gault equation allows us to predict the creatinine clearance (and therefore renal function/gfr) for patients differing in age and weight. For male patients, Cl creat (140 age) weight (male) = 72 Cp creat where age is in years, weight is in kg, and Cp creat is in mg/dl. The Cl creat is then in ml/min. This is an empirical equation which works only if the age, weight, and Cp creat (or Scr) are entered in the units specified. For the 30 y.o. (140 30)(70) Cl creat = = ml/min (72)(1) Although clearance is expressed in volume-per-time, the amount of creatinine eliminated-per-time may be found using the creatinine concentration given: Creatinine cleared per hour = 60min 10dL 1L (106.94ml/ min)(1mg/dl) 1hr 1L 1000ml = 64.2 mg/hr (so in 1 day, about 1.54 g of creatinine is lost which is balanced by eating and producing 1.54 g of creatine per day)) For the 75 y.o. (140 75)(70) Cl creat = = 63.2ml/min (72)(1) Creatinine cleared per hour =

3 60min 10dL 1L (63.2ml/min)(1mg/dL) 1hr 1L 1000ml = 37.9 mg/hr (Remember, elderly have less muscle mass which means less creatinine production)

4 3. J.R., is a 65-year-old, 65kg patient with a serum creatinine of 1.0mg/dL. For several weeks he received tablets of 375 µg of digoxin per day to treat his CHF. Assume that this patient cannot take anything by mouth anymore and he must be converted to daily intravenous doses of digoxin. Calculate an intravenous dose equivalent to the 375 µg tablets he ingests daily Amount of drug absorbed = F Dose = µg = µg The intravenous dose should be µg

5 4. Oxazolidinone antibiotics are a new synthetic class of antibacterial agents. The FDA recently approved Linezolid, an oxazolidinone antibiotic. Administration of this antibiotic may cause gastrointestinal distress that is eliminated when taken with food. However, the presence of food may reduce bioavailability. Given the following data, determine the absolute bioavailability of 375 mg Linezolid tablets with and without food. Does food affect bioavailability? Time [hrs] C p C p C p after i.v.[µg oral [µg/ml] food oral [µg/ml] i.v.[µg oral[µg oral after food [µg C 14 /k e = Calculate the k e from the terminal portion of each concentration time profiles. C ln( 12 ) C ln( ) ln( ) ln( ) k e = = = 0.20hr or = 0.20hr or = 0. hr Bioavailab ility( F) = PO IV

6 Fasted ( F) = = Fed ( F) = =

7 5. Given the data below for two prednisolone tablet formulations, are these products bioequivalent? What pharmacokinetic criteria did you use to draw this conclusion? Product A Product B Ratio (%) A/B 90% Confidence Limits 0-15 h (µg min/ml) 0- (µg min/ml) C MAX (ng/ml) T MAX (h) T 1/2 (min) Bioequivalence is determined by the 0-15 h 0- and C MAX. The 90% confidence limits of the RATIO of product A/Product B must fall within %). From this data, you would conclude that these two tablets are bioequivalent.