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Dosing Regimen Concepts Applications Practice Problems Discussion True or False ? Accumulation always occurs. Time to reach the plateau depends on the frequency of drug administration. The extent of accumulation increases when the drug is given less frequently. At plateau, the amount of drug lost within a dosing interval equals the oral maintenance dose. True or False ? The larger V, the smaller Css,av Css,av depends on the absorption kinetics of the drug. The faster drug is administered, the shorter the time to steady state. AUC0- after a single dose is equal to AUC at steady state. During an infusion at steady state, rate in equals a. rate out b. rate out c. rate out d. rate out e. all of the above If the plasma concentration of a drug is measured after its infusion to steady state, the clearance value is calculated from a. Dose/AUC b. KEV c. Ko / Css d. (ln 2) V / t1/2 e. any of the above Amikacin Cyclophosphamide Dexamethasone CL [L/h] 5.5 5.5 16 V [L] 19 56 56 If the above drugs were administered by infusion at the same rate until steady state a. Amikacin and Cyclophosphamide would have the same Cp,ss. b. Amikacin and Dexamethasone would have the same Cp,ss. c. Cyclophosphamide and Dexamethasone would have the same Cp,ss. d. they would all have a different Cp,ss. e. none of the above. Amikacin Cyclophosphamide Dexamethasone CL [L/h] 5.5 5.5 16 V [L] 19 56 56 If the above drugs were administered by infusion at the same rate until steady state a. Amikacin and Cyclophosphamide would have the same Ass. b. Amikacin and Dexamethasone would have the same Ass. c. Cyclophosphamide and Dexamethasone would have the same Ass. d. they would all have a different Ass. e. none of the above. Which of the following is not a determinant of the steady-state concentration? a. V b. CL c. t1/2 d. Ko e. none of the above Which of the following pharmacokinetic parameters can be calculated if plasma concentration-time data are available during infusion (Ko known) to steady state ? a. V b. CL c. KE d. t1/2 e. all of the above The following five drugs were all administered at the same rate of infusion, Ko. Fill in the missing values in the Table below. Drug CL V t90%ss Css Ass [L/h] [L] [h] [mg/L] [mg] A 20 50 B 20 100 C 20 25 D 40 50 E 10 50 10 Drugs A and B have the following CL (L/h) values; if both drugs were infused at the same rate, Ko CL V A 5 50 B 10 50 a. A would reach steady state faster than would B. b. A would have a higher steady state plasma concentration than would B. c. B would have a higher steady state body level than would A. d. B should have a loading dose administered; A should not. e. A should be formulated in a sustained release preparation if it were to be given orally. Ceftriaxone t1/2 = 7.3 h and V = 11.5 L If an i.v. infusion of 100 mg/h has been running for 5.5 h, what would be the Cp ? Ceftriaxone t1/2 = 7.3 h and V = 11.5 L What will be the value of Cp,ss ? How much more time will pass (t = 5.5 h now) before 90% of Cp,ss is achieved ? Ceftriaxone t1/2 = 7.3 h and V = 11.5 L If at t = 5.5 h into the infusion we want to go immediately to steady state, how much ceftriaxone should be administered immediately ?