Multiple Dosing

Question 1

IV Injection Variables

Answer 1

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

Question 2

(X1)max

Answer 2

= Dose

Question 3

(X1)min

Answer 3

= Dose * e^(-KT)

Question 4

(X2)max

Answer 4

= Dose + Dose * e^(-KT)

Question 5

Dost Ratio

Answer 5

r = (1 - e^-(nKT)) / (1 - e^(-KT))

Question 6

(Xn)max

Answer 6

Dose * r

Question 7

Before Steady State Equations - IV

Answer 7

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)

Question 8

At Steady Use State Equations - IV

Answer 8

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)

Question 9

Why is concentrations at steady state more useful?

Answer 9

Important to know for therapeutic window

Question 10

Accumulation Ratio (R)

Answer 10

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

Question 11

Fraction of Steady State

Answer 11

• 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

Question 12

Half Lives + Css Percent

Answer 12

3. 32 half lives = 90% Css
4. 32 half lives = 95% Css
5. 65 half lives = 99% Css

Question 13

Average Concentration at Css - IV

Answer 13

Css,avg = Dose / VKT

Question 14

Loading Dose - IV

Answer 14

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

Question 15

Designing Dose Regimen (6)

Answer 15

1. Determine therapeutic of effective concentration range for drug
2. Choose desired Css,avg for plasma concentration - usually the midpoint of the therapeutic range
3. Select dosing interval (usually equal to drug’s half life) needed to attain desired Css,avg - Dose = Css,avg * VKT
4. Round off number for calculated dose and chosen dosing interval - can round to nearest whole number or closest commercially available product
5. Using rounded numbers, calculate “average” Css, peak Css, and trough Css - insure that peak and trough are still in therapeutic range
6. If necessary, make small adjustments (fine tuning) in the dose and dosing interval.

Question 16

Multiple Oral Dosing Equation

Answer 16

• 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

Question 17

Oral Loading Dose

Answer 17

-Also must have absorption component

DL = Dose * ( 1 / (1 - e^(-KT)) * (1 - e^(-kaT)))

Question 18

Css,avg - Oral

Answer 18

Css,avg = F * Dose / VKT

Question 19

Accumulation Factor - Oral

Answer 19

R = Css / C1 = 1 / 1 - e^(-KT)

Question 20

Intermittent IV Infusion

Answer 20

• 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

Question 21

Intermittent IV Concentration Equation

Answer 21

C = Ro/VK * (1 - e^(-Kt)) * [(1 - e^(-nKT)) / (1 - e^(-KT))] * e^(-KT)

Question 22

Oral/Intermittent Cmax, Cmin, tmax, etc. Equations

Answer 22

• 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