3 Clinical psychopharmacology3.2 Pharmacokinetics
3.2.1.2 Effect of mode of administration on kinetics
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Written by Resident Doctor Committee · Published
First-pass metabolism and bioavailability
An intravenous dose reaches the circulation in full, so its bioavailability is 100% by definition and it is the reference for every other route.
Oral dosing gives the greatest first-pass metabolism of the common routes, because absorbed drug reaches the liver through the hepatic portal vein before the systemic circulation.
Routes that drain into systemic veins rather than the portal circulation, such as transdermal and sublingual, avoid first-pass hepatic metabolism.
Intravenous antidepressants need a lower dose than oral ones, because they bypass gut absorption and first-pass loss.
Comparing the routes
Route | Absorption and consequence |
|---|---|
Oral | Gut uptake, then first-pass loss; food and formulation alter it |
Sublingual or buccal | Rapid mucosal uptake; swallowed drug still undergoes first pass |
Rectal | Mixed portal and systemic drainage, so absorption varies |
Intramuscular | Aqueous injections are absorbed rapidly; depots release slowly |
Subcutaneous | Often slower, depending on local perfusion |
Transdermal | Sustained skin diffusion; a skin reservoir delays onset and offset (rivastigmine) |
Inhaled | Potentially rapid pulmonary uptake |
Antidepressants by other routes
Route | Antidepressant |
|---|---|
Intravenous | Citalopram, the only selective serotonin reuptake inhibitor (SSRI) with an intravenous formulation |
Sublingual | Fluoxetine, the only SSRI with reported evidence of efficacy by this route |
Rectal | Sertraline |
Transdermal | Selegiline, the only antidepressant made as a patch |
The lowest selegiline patch dose needs no tyramine diet, because the patch avoids first-pass metabolism and spares gut monoamine oxidase A.
Long-acting injectable antipsychotics
Depot release is prolonged and cannot be reversed, so adverse effects can persist after injections stop.
Feature | First-generation depots | Second-generation long-acting injections |
|---|---|---|
Examples | Zuclopenthixol, flupentixol, haloperidol and fluphenazine decanoate | Paliperidone palmitate, risperidone, aripiprazole |
Test dose | Needed before regular dosing; 100 mg for zuclopenthixol decanoate | None; paliperidone palmitate starts once oral paliperidone or risperidone has been tolerated |
Zuclopenthixol decanoate alone among first-generation depots has randomised trial evidence of better relapse prevention, possibly at the cost of more extrapyramidal effects; the other three are equivalent to one another.
Tardive dyskinesia risk follows cumulative dopamine blockade, so it is comparable for the depot and oral forms of the same drug.
Olanzapine embonate (pamoate) can cause post-injection delirium/sedation syndrome when accidental intravascular entry dissolves the salt rapidly, so observation after every injection is mandatory.
The syndrome brings abrupt sedation, confusion, dysarthria and ataxia within an hour.
Clozapine has no depot.