Multiple Dosing Flashcards
IV Injection Variables
Tau (T) - Uniform dosing interval
(Xn)max = amount of drug in body immediately after injection of nth dose
(Xn)min = amount of drug in body T hours after nth dose
K = first order rate constant for overall loss from body
(X1)max
= Dose
(X1)min
= Dose * e^(-KT)
(X2)max
= Dose + Dose * e^(-KT)
Dost Ratio
r = (1 - e^-(nKT)) / (1 - e^(-KT))
(Xn)max
Dose * r
Before Steady State Equations - IV
Cn = Dose/V * (r * e^-(Kt))
0 < t < T (or equal to)
(Cn)max = Dose/V * (1 - e^ (-nKT) / 1 - e^(-KT))
(Cn)min = (Cn)max * e^(-KT)
At Steady Use State Equations - IV
Css,max [n = infinity, t=0]
Css,max = Dose/V * (1 / 1-e^(-KT))
Css,min [n= infinity, t = T]
Css,min = Css,max * e^(-KT)
Why is concentrations at steady state more useful?
Important to know for therapeutic window
Accumulation Ratio (R)
R = Css,max / (C1)max = 1 / 1 - e^(-KT)
- Gives extent drug would accumulate in body following fixed dose regimen
- Dependent on elimination constant and half life ONLY
- Independen of dose
- Multiplying R by mix, max, average concentrations will approximate their values at steady state
Fraction of Steady State
- Identical to continuous infusion equation
- tss = times required to reach fraction of Css
- Solely function of half life
- Independent of number of doses or dosing interval
Half Lives + Css Percent
- 32 half lives = 90% Css
- 32 half lives = 95% Css
- 65 half lives = 99% Css
Average Concentration at Css - IV
Css,avg = Dose / VKT
Loading Dose - IV
DL = Dose * (1 / 1 - e^(-KT))
- If chose properly, (C1)max = Css,max
- Administration of DL followed by maintenance dose every T hours should produce and maintain Css
- DO NOT ADMINISTER DL AND DOSE @ T INTERVALS SIMULTANEOUSLY, RISK OVERDOSING PATIENT
Designing Dose Regimen (6)
- Determine therapeutic of effective concentration range for drug
- Choose desired Css,avg for plasma concentration - usually the midpoint of the therapeutic range
- Select dosing interval (usually equal to drug’s half life) needed to attain desired Css,avg - Dose = Css,avg * VKT
- Round off number for calculated dose and chosen dosing interval - can round to nearest whole number or closest commercially available product
- Using rounded numbers, calculate “average” Css, peak Css, and trough Css - insure that peak and trough are still in therapeutic range
- If necessary, make small adjustments (fine tuning) in the dose and dosing interval.
Multiple Oral Dosing Equation
- Crazy long equation, same as oral concentration except the r portion has a ka portion
- Must have absorption constant in equation now as well since not immediately available like IV
Oral Loading Dose
-Also must have absorption component
DL = Dose * ( 1 / (1 - e^(-KT)) * (1 - e^(-kaT)))
Css,avg - Oral
Css,avg = F * Dose / VKT
Accumulation Factor - Oral
R = Css / C1 = 1 / 1 - e^(-KT)
Intermittent IV Infusion
- Series of short, successive (<30 mins) IV Infusions
- Time of drug elimination allowed between infusions
- Drug concentration does not reach Css during initial infusions
- Used to prevent high, transient drug concentrations and related side effects
- Many drugs are better tolerated when infused slowly over time compared to IV bolus
Intermittent IV Concentration Equation
C = Ro/VK * (1 - e^(-Kt)) * [(1 - e^(-nKT)) / (1 - e^(-KT))] * e^(-KT)
Oral/Intermittent Cmax, Cmin, tmax, etc. Equations
- Too long to write on these flashcards
- Will be provided on equation sheet
- Make sure you recognize which ones are which and input them into calculator one part at a time
