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Last edited: 7/31/2022

PHARMACOKINETICS | DRUG DISTRIBUTION

Pharmacokinetics | Drug Distribution Medical Editor: Dr. Ana Guerra

OUTLINE
I) DRUG DISTRIBUTION (D) SOLUBILITY
II) FACTORS AFFECTING (E) VOLUME OF DISTRIBUTION
DISTRIBUTION III) REVIEW QUESTIONS
(A) BLOOD FLOW IV) REFERENCES
(B) CAPILARY PERMEABILITY
(C) PROTEIN BINDING

I) DRUG DISTRIBUTION
The process of which the drug gets distributed from the bloodstream throughout the different tissues of the body.

II) FACTORS AFFECTING DISTRIBUTION

(A) BLOOD FLOW
(1) Organs with an increase blood flow (2) Organs with a decrease blood flow

(i) Brain (i) Skin

(ii) Liver (ii) Adipose tissue
(iii) Kidneys

(3) Clinical correlation

(i) Shock
o Regardless the etiology, a shock usually leads to a decrease in blood flow

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 (B) CAPILARY PERMEABILITY

(1) Fenestrated or sinusoidal capillaries (C) PROTEIN BINDING

(1) Albumin

(i) Liver
(ii) Bone marrow
(iii) Spleen
(iv) Kidneys (i) With high protein bound drugs
(v) Glands o Less amount of free drugs into the blood stream

(2) Continuous capillaries or BBB

Diffusion of drugs out of the blood stream and into the

tissues depend upon two factors:
a. Transporters (ii) With poor protein bound drugs
b. Hydrophobic drugs
o Large amount of free drugs into the blood stream
(i) Central nervous system (BBB)
(ii) Muscle

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(2) Clinical correlation

(3) Clinical correlation (i) Patients with chronic kidney disease

o Loss of albumin in the urine
(i) Septic Shock

(ii) Patients with liver failure

o Less production of albumin

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(D) SOLUBILITY

(i) Small nonpolar hydrophobic drugs

(ii) Large polar hydrophilic drug

(iii) Drugs bound to albumin

(E) VOLUME OF DISTRIBUTION

a. If a drug can occupy the three compartments of the body (bloodstream, interstitial fluid and intracellular fluid) it would have
a high volume of distribution.
b. If can only occupy the plasma it would have a low volume of distribution.

(1) Low volume of distribution

(i) Warfarin
a. Plasma protein binding drugs
b. Large polar hydrophilic drugs
c. Low blood flow to particular organs
d. Poor capillary permeability

(2) Medium volume of distribution

(3) High volume of distribution

a. Free drugs
b. Small nonpolar hydrophobic drugs
c. Large amount of blood flow
d. Increased capillary permeability

(i) Chloroquine

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III) REVIEW QUESTIONS

1) NN610 is an investigational cholesterol-lowering
agent. Has a high molecular weight and is
extensively bound to albumin. NN will have a _____
apparent volume of distribution (Vd)
a) High
b) Low
c) Extremely high
d) Normal
2) A 40-year-old male patient (70 kg) was recently
diagnosed with infection involving methicillin-
resistant S. aureus. He received 2000 mg of
Vancomycin dose. The peak plasma concentration of
Vancomycin was 28.5 mg/L.
The apparent volume of distribution is:
a) 1 L/kg
b) 7 L/kg
c) 10 L/kg
d) 14 L/kg
e) 70 L/kg
3) Levodopa is a drug very commonly used to treat
Parkinson’s disease that acts by being converted to
dopamine in the brain. Which property should it have
in order to being able to cross the BBB?
a) Large and polar
b) Large and nonpolar
c) Hydrophobic
d) Bound to proteins
4) What is the formula to determine Vd of a drug?
a) Vd = F x dose / C
b)Vd = F / dose x C
c)Vd = C x F / C
d)Vd = F + dose / C

IV) REFERENCES
● UpToDate 2022

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