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Pharmacokinetic Modeling (describing what happens)

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Pharmacokinetic Modeling

(describing what happens)

- AKA “Apparent volume of distribution”
- The volume of fluid that appears to contain the amount of drug in the body
- May not be actual physiologic space(s)

- Relates amount to plasma concentration
- The volume that must be processed by organs of elimination

- Equations
- Experimentally:
- Vz = Dose / Cp0

- Intellectually:
- Vz = Amount in the body / Cpt

- Experimentally:
- Units
- Liters or milliliters (whole animal or human beings)
- Liters/kg or milliliters/kg (typical vet med)

- Give IV Bolus
- Take samples over time
- Cp0 is Y axis interecept
- You know the dose

- Vz = Dose / Cp0

Much like row 4 of table

Much like row 2 or 3 of table

- The volume of plasma water cleared of drug during a specified period of time

- Organ clearance is:
- Efficiency X Flow (fraction of drug removed X organ flow)
- Clearance = Q x E

- Efficiency X Flow (fraction of drug removed X organ flow)
- Total clearance is:
- The sum of all organ clearances
- Cl total=Cl hepatic + Cl renal + Cl pulmonary

- The sum of all organ clearances
- Experimentally:
- Clearance = Vz x λz

- I know it’s weird but:
- At a particular concentration, extracting ½ the drug from ALL the flow is the same thing as extracting ALL the drug from ½ the flow
- (We “clearance” not “amount removed” because it works int with the samples we take and the math we can do).

- At a particular concentration, extracting ½ the drug from ALL the flow is the same thing as extracting ALL the drug from ½ the flow

0% cleared from

0.5 ml.

200 µg/ml

(1 ml)

100 µg/ml

(1 ml)

Passes through liver in

1 minute

100 % cleared from

0.5 ml.

Clearance is 0.5 ml/min

- Units
- Volume / unit time (l/hr, l/min, ml/min, etc.)
- Whole animals or human beings

- Volume / kilogram / unit time
- Animals

- Volume / unit time (l/hr, l/min, ml/min, etc.)

- The fraction of the volume of distribution cleared per unit time.
- The slope of the natural log plot of drug concentration verus time profile.

Concentration vs time points represent concentrations determined for samples taken from the tank.

- The time for elimination of one half of the total amount in the body
- Equation:
- T1/2 = 0.693/λz (elimination rate constant)

- Units:
- Time (hours, minutes, seconds…)

- Utility
- Tissue Residues
- At 5 x T1/2 (after you stop dosing) 97% has been eliminated.
- Make sure you use the longest half-life
- Metabolites MAY be more important than the drug
- Absorption may have the longest half-life.

- At 5 x T1/2 (after you stop dosing) 97% has been eliminated.

- Tissue Residues

- Utility
- Approach to “Steady state”
- Drugs with long half-lifes “accumulate” during repeated administration
- A 5 x T1/2 concentrations reach 97% of steady state
- Digoxin – maximum effects 8 days after therapy starts

- Need for loading dose
- A loading dose is an initial dose given to shorten the time it takes to reach steady state (“load” the body to steady state amounts and concentrations).

- Approach to “Steady state”

- Fractional rate at which drug moves from the place the dose was put INTO the circulatory system.
- Units
- Time (hours, minutes, seconds…)

- Application
- Combined with elimination rate, determines time to reach peak concentration (C max)

- Other than IV, it is rare that the ENTIRE dose is actually absorbed
- Oral
- Destroyed, eliminated unchanged

- IM
- Hydrolyzed in tissue, bound to tissues, stuck in abscess

- Oral
- Units
- Percentage or decimal (80% = 0.8)

- Bioavailability

Two oral dose forms of the same drug. F of the “open triangle” dose form is ½ the “filled triangle” dose form.

- Bioavailability and Bioequivalence

Equal bioavailability (same F) and Bioequivalent

Equal bioavailability (same F) and not Bioequivalent