Two drugs bind to the same receptor. Drug A exhibits an of 15%, an of 5 nM, and a Hill coefficient of 2.1, whereas Drug B exhibits an of 95%, an of 80 nM, and a Hill coefficient of 0.5. Based on these pharmacodynamic properties, which statement is TRUE?

Patient B.T. was treated with carbamazepine. A dosage regimen of 125 mg twice daily produced a steady-state plasma concentration of 6.75 mg/L. Increasing the regimen to 150 mg three times daily resulted in a steady-state plasma concentration of 17.9 mg/L. Assuming that carbamazepine exhibits nonlinear pharmacokinetics due to saturable metabolism and that its volume of distribution and oral bioavailability are dose-independent, answer the following questions.(14 pts. total) a. Calculate (i) Km and (ii) Vmax. (2 pts. each) b. Calculate the daily dose (DR) of carbamazepine required to achieve a target steady-state plasma concentration (Css) of 20 mg/L in Patient B.T.. (2 pts.) c. Following more than one month of therapy at the calculated maintenance dose (as calculated in b.), Patient B.T.’s carbamazepine Css declined from 20 mg/L to 4 mg/L due to autoinduction of metabolism. (i) Calculate the post-induction values of Km and Vmax. If a parameter remains unchanged, indicate “no change”. (2 pts. each) (ii) Calculate the revised daily dose required to maintain a of 20 mg/L. (2 pts.) (iii) Determine the carbamazepine elimination half-life corresponding to the revised dosing regimen, assuming the apparent volume of distribution of carbamazepine is 100 L. (2 pts.)

For a drug administered repeatedly, suppose the dosing interval (τ) is reduced while the bioavailability (F), dose (D), volume of distribution (V), and elimination rate constant (k) remain unchanged. What effect will this have on the fluctuation between the steady-state peak and trough plasma concentrations?

The standard oral dosing regimen of metronidazole for the treatment of intra-abdominal infections in adults is 500 mg every 6 hours. In the general adult population, metronidazole has an elimination half-life (t1/2) of 2.5 hours and an apparent total clearance (CL/F) of 20.8 L/h. (20 pts. total) a. Using the standard oral metronidazole regimen of 500 mg every 6 hours in the general adult population, calculate:  (i) Maximum steady state concentration (3 pts.) (ii) Minimum steady state concentration (1 pt.). b. Patient C.Y., who has an intra-abdominal infection, has been receiving metronidazole 400 mg orally every 6 hours for several days. At steady state, the measured trough plasma concentration (Css,min) was 4.78 mg/L. Assuming that the apparent volume of distribution (V/F) in Patient C.Y. is the same as the average value in the general adult population, calculate the elimination rate constant (k) of metronidazole in Patient C.Y. (3 pts.) c. Design a practical oral dosing regimen (i.e., the dose and dosing interval) for Patient C.Y. that will achieve the same therapeutic exposure as the standard 500 mg every 6 hours regimen in the general adult population. (10 pts.) d. Is a loading dose needed for Patient C.Y.? If yes, calculate the loading dose. (3 pts.)

At distribution equilibrium and in the absence of active transport, Drug A is 24% plasma protein bound. Given a total plasma concentration of 105 mg/L and a total tissue concentration of 180 mg/L, what is its fraction unbound in tissue (fu,T)?

For an intravenously infused drug that follows one-compartment pharmacokinetics with zero-order input and first-order elimination, which of the following statements is true?

Which of the following statements about flip-flop kinetics is correct?

In the case of perfusion rate-limited distribution, which of the following changes is most likely to reduce the rate of drug entry into tissues?

When distribution equilibrium has been reached and active transport does not contribute to drug distribution, increasing plasma protein binding will result in an increase in:

Patient W.L. received a 20 mg intravenous (IV) bolus dose of pamidronate for the treatment of Paget’s disease of bone. Plasma samples were collected 15 minutes and 5 hours after administration. The measured plasma concentrations were: C15min = 76.6 µg/L, C5h = 68.1 µg/L. Assume that pamidronate follows a one-compartment pharmacokinetic model with first-order elimination. (17 pts. total) a. To improve therapeutic response, the physician decides to administer pamidronate by continuous IV infusion and wishes to achieve a target steady-state plasma concentration (Css) of 200 µg/L. Calculate the IV infusion rate required to achieve the desired steady-state concentration in this patient. (9 pts.) b. Calculate the plasma concentration of pamidronate 4 hours after the IV infusion is initiated. (2 pts.) c. One month later, Patient W.L. returns for a second treatment course. Due to a severe intra-abdominal infection, his renal function has declined, and his creatinine clearance (CrCL) has decreased from 110 mL/min to 65 mL/min. Assume that 46% of an IV dose of pamidronate is excreted unchanged in urine. To maintain the target Css of 200 µg/L, calculate the following: (i) IV infusion rate (4 pts.); (ii) Loading dose (2 pts.).