L70: Practical Pharmacokinetics

Question 1

One-compartment vs Two-compartment vs Multiple-compartment model

Answer 1

One-compartment:

• drug instantaneously distribute throughout the body
• monophasic response
• log C-t graph —> 直線
• First-order reactions

Two-compartment:

• Central + peripheral compartment
• Central: highly perfused; Peripheral: less perfused
• does not achieve instantaneous distribution
• Initial rapid decline: elimination from central compartment + distribution to peripheral
• Then achieve distribution equilibrium: only elimination from central compartment
• Biphasic response
• log C-t graph: 兩條直線
• First-order reactions

Multiple-compartment:
- multiple phases: 多條直線

Question 2

Homogenous reaction vs Heterogeneous reaction

Answer 2

Homogenous: only single phase —> proceed uniformly throughout whole system

Heterogeneous: more than one phase (change of state: tablet to solution) —> rates depend on supply of fresh reactant to the phase boundary

Question 3

***Zero order, First order, Second order process

Answer 3

Zero:

• rate = -k (rate independent of C)
• C = Co - kt
• half-life: Co/2k

First: (decomposition of drugs)

• rate = -kC (rate depend on C)
• lnC = lnCo - kt
• **- half-life: 0.693/k (independent of dose)

Second: (depend on 2 concentration terms)

• rate = -kC^2 (rate depend on C^2)
• 1/C = 1/Co + kt
• half-life: 1/(kCo)

Question 4

Volume of distribution

Answer 4

Fluid volume that would be required to contain all drugs in the body at the same concentration as in the plasma

V = amount of drug / Cp

If exclusively bound to plasma protein —> V will be near to plasma volume
High value: distribute to muscle / tissue

V Depends on:

1. Degree of binding to plasma/tissue protein
2. Partition coefficient
3. Age, gender, body composition, disease etc.

Question 5

***Clearance and Steady state, maintenance dose, loading dose

Answer 5

Elimination of drugs follows first order —> then zero order when saturated
Rate of drug administration = rate of drug elimination
1. F x dosing rate = CL (clearance) x Css (steady state concentration)

2. CL = Rate of elimination/C = Dose/AUC (total amount of drug accumulated)
3. CL = CL(renal) + CL(hepatic) + CL(other)
4. Rate of elimination = Q (bloodflow) x (Ca-Cv)
5. CL(organ) = Q x (Ca-Cv/Ca) = Q x E (excretion ratio)
6. Maintenance dose: F x Dosing rate = CL x Target C
   - Cssmax = F x Vss/ Dose / 1-e^-kt
   - Cssmin = F x Vss/ Dose / 1-e^-kt x e^-kt
7. Loading dose: F x Loading Dose = Vss x Target C
8. Half-life = 0.693 Vss/CL
   —>***CL = 0.693 Vss / half-life

Question 6

Renal clearance depends on

Answer 6

Filtration, active secretion and reabsorption

Rate of secretion depends on:

1. Drug binding to plasma protein
2. Degree of saturation of transporter
3. Rate of delivery of drug to site of secretion