Predicted Steady State Concentration & Plasma Level

Questions 1 through 3 A medication with a clearance of 12 L/hr and volume of distribution of 104 L is administered to a patient (80kg) as an intravenous infusion. The infusion rate is 80 mg/hr. The medication is 95% bound to plasma. 1. How long will it take to reach a steady state after the start of the infusion? 2. What is the predicted steady-state concentration? 3. Assuming that the infusion was terminated after only 2 hours, what is the estimated plasma level 4 hours after the infusion is terminated? Questions 4 through 7 LIU-444 is a new experimental medication. The medication has a reported volume of distribution of 300 L and a clearance of 11 L/hr. Less than 10% of the drug is excreted unchanged by the kidney. The recommended dose is 0.6 mg/kg administered by IV bolus every 24 hours. Assume a body weight of 70 kg. LIU-444 is 95% bound to plasma proteins. 4. Calculate the predicted maximum plasma concentration at steady state for LIU-444. 5. Calculate the predicted minimum plasma concentration at steady state for LIU-444. 6. What is the predicted average amount of drug in the body at steady state for this dosing regimen? 7. Would a change in plasma binding (e.g., due to a drug:drug interaction that increased fu), be expected to be clinically relevant for LIU-444? Please answer YES or NO Questions 8 through 10 The table below contains plasma concentrations vs. time data from a patient (68 Kg) who received a continuous infusion of a new medication, HDT-326. The infusion rate was 30 g/Kg/hr over a period of 24 hours. When the data in the table is plotted (C vs. time), it follows the shape of the graph provided. 8. Calculate clearance, volume of distribution, half-life, and k 9. The minimum effective plasma concentration of this medication is 10 ng/ml. Assuming the infusion was terminated after 24 hours, how long would the medication continue to be therapeutically effective (after stopping the infusion)? 10. Estimate the loading dose that would immediately produce a steady state level in this patient. The table below was obtained from a crossover clinical trial evaluating the pharmacokinetics of several different formulations of cibenzoline (CBZ). The values presented are the mean data from 18healthy volunteers. Formulation ID I Active Ingredient (strength)* CBZ (160 mg) II CBZ (160 mg) III IV CBZ (160 mg) CBZ (100 mg) Dosage Form Immediate Release Tablet Immediate Release Capsule Oral Solution IV Solution tmax (hr) 2 AUC0- (ug-hr/L) 3100 1.5 3300 — 3400 2500 1 *strength refers to the amount of active ingredient in the formulation 1. Which formulations in the table are pharmaceutically equivalent? 2. Which oral dosage form has the slowest rate of absorption? 3. What is the difference between absolute and relative bioavailability? 4. What is the calculated absolute bioavailability of the capsule dosage form?