New Material Flashcards
The drug fraction REMAINING from initial concertation at any time after the dose is represented by the expression
e^-kt
What is each subsequent dose additively influences the total plasma concentration
The principle of superposition
What is the PK profile is a series of peaks (Cmax) and troughs (Cmin)
Fluctuation
Accumulation depends on the dosing interval (t) relative to the drug’s
Half-life
At steady-state, the peaks and troughs are the same for
Successive doses
The time difference between Cmax amd Cmin =
Tau
A patient is to be given gentamicin IV to achieve steady-state peaks and troughs of 8 and 0.5 mg/L. The patient is estimated to have the following PK parameters: Vd =17.5 L and t1/2 = 2 h.
If multiple doses are to be given, determine a suitable dose and dosing interval for this patient.
131 mg
What are the TYPICAL IV DOSING
INTERVALS
4,6,8,12,24 h
A new drug has a very narrow therapeutic range (12–25 mg/L). The goal is to design a dosing regimen that will result in a steady-state peak and trough of 20 and 14 mg/L, respectively. The drug’s elimination rate constant has a population average value of 0.043 h−1. What dosing interval is needed to provide the desired steady-state peaks and troughs?
8h
A patient is to be given gentamicin IV to achieve steady-state peaks and troughs of 8 and 0.5 mg/L. The patient is estimated to have the following PK parameters: Vd =17.5 L and t1/2 = 2 h.
If multiple doses are to be given, determine a suitable dose and dosing interval for this patient.
8h
A patient is receiving 1000 mg of sulfamethoxazole IV every 12 hours. At steady state, the max and min plasma concentrations were 81.5 and 40 mg/L, respectively. What is the volume of distribution of sulfamethoxazole in this patient?
24 L
What are the PK profile features of multiple oral doses?
- Fluctuation
- Delayed Cmax due to absorption
- Accumulation
- about 5 half-lives to steady state
What is a parameter used to quantify the ultimate amount of drug accumulation in the body at steady-state (Ra)
Accumulation factor
What compares the steady state plasma concertation to the equivalent concentration after the first dose:
Accumulation factor
If administered every half-life, there will be _____ times more drug in the body at SS then after a single dose
1.44
The average Cp ss is ______ the arithmetic mean of the max and min Cp at steady state
NOT
At steady state, plasma drug concentrations fluctuate around the average ____ during multiple drug administration
Cp
Consider the following dosing regimens of the same drug (F = 1):
100 mg Q 4h
200 mg Q 8h
300 mg Q 12h
Would all of these regimens provide the same dosing rate (FD/t)?
yes all are 25
Multiple Oral Drug Administration: ModelAssumptions
Compartment open model?
One-compartment open model
Multiple Oral Drug Administration: ModelAssumptions
Rate of drug absorption?
Is rapid (no lag time) and follows first-order kinetics
Multiple Oral Drug Administration: ModelAssumptions
When each doses is administered?
Each dose is administered after the majority of the previous dose is absorbed
Multiple Oral Drug Administration: ModelAssumptions
What factor is considered?
Bioavailability factor (F)
Multiple Oral Drug Administration: ModelAssumptions
Predicted peak and trough concentrations?
The predicted peak and trough concentrations are NOT accurate
Multiple Oral Drug Administration: ModelAssumptions
Elimination order?
Elimination is first-order process
What are the 3 impacts of the Drug Absorption Rate on the Predicted Plasma Concentrations
- A faster absorption rate yields more accurate prediction
- A slower absorption rate results in an overestimation of Cmax
- Absorption rate has a negligible impact on Cmin
Given parameters: Vd = 80 L, CL = 20 L/h, t1/2 = 4 h, and F = 0.85,
Cmax ss= 50 ug/L, Cmin ss = 25 ug/L.
Dose - ?
Dosing interval - ?
Cp ss av - ?
Dose: 2353 micrograms
Dosing interval: 4 h
Cp ss av: 0.036 mg/L
What is the key mechanism of nonlinear PK behavior?
The concentration-dependent saturation of a carrier or enzyme involved in the drug ADME processes.
Nonlinear PK implies a
Dose- or time-dependency of PK processes
For nonlinear PK’s what 3 things depend on the dose of the drug?
CL
Half-life
F
For nonlinear elimination CL and t1/2 are concentration
Dependent
Doubling the dose of the drugs that follow nonlinear PK may more than double the
Cp
The most clinically important type of nonlinear pharmacokinetics is _________ metabolism
satuarble
All active drug transport processes are capacity limited (saturable) and exhibit what kinetics?
Michaelis-Menten kinetics
Km =
the Michaelis-Menten
constant (the concentration that produces 50% of VMAX)
Michaelis-Menten Kinetics use what 3 orders?
- 1st order
- Mixed order
- Zero order
At high concentrations
(C»_space; Km), Vmax =
Amount of the drug removed per unit time
A patient has been using phenytoin 100 mg three times daily. The phenytoin level was drawn and found to be 8.8. ug/mL (reference range 10-20 ug/mL). The prescriber doubled the dose to 200 mg three times daily. The patient started to slur her words, felt fatigued and returned to the clinic. The level was repeated and found to be 23.7 ug/mL. Which of the following statement is accurate regarding the most likely reason for the change in phenytoin level?
a. Phenytoin half-life is reduced at higher doses.
b. Phenytoin volume of distribution increases at higher doses.
c. Phenytoin bioavailability can decrease at higher doses.
d. Phenytoin metabolism can become saturated at higher doses.
d
Drug T has a VMAX of 600 mg/d and a KM of 12 mg/L. What is the clearance for Drug T when C = 100 mg/L
5.4 L/day
Known parameters: Cpss = 15 mg/L Vmax = 400 mg/day
Km = 4mg/L, S = 0.92, F=1
Dosing Rate - ?
343 mg/day
