Distribution of drugs

Perfusion and drug distribution

• Highly perfused tissues receive a disproportionately large amount of drug
  --> Acts as reservoir
• When plasma concentration drops below the concentration in these tissues
  --> Drugs redistributes from highly perfused tissues to less well perfused tissues

Lung

• Highly perfused
• High uptake, especially for basic lipophilic amine (pK8)
  * e.g. lidocaine, propanolol, meperidine, fentanyl, sufentanil, alfentanil
  * First-pass pulmonary uptake >65% of doses

CNS

Ionised

• Ionised water-soluble drugs
  --> Entry into CNS restricted due to blood-brain barrier
  * Can be overcome by large dosage
  * BBB may be disrupted by acute head injury or arterial hypoxemia

Non-ionised

• Nonionised lipid-soluble drugs
  --> Entry into CNS limited only by cerebral blood flow

High dose and redistribution

• When dosage is high
  --> Less well perfused tissues become saturated
  --> No more redistribution
  * Example: thiopentone, fentanyl

Thus,

• Metabolism becomes the only mechanism for drug level to decrease
  --> Drug level only falls slowly