Distribution of drug after administration

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