Non-oral extravascular routes, which encompass sublingual, buccal, topical, intramuscular, and inhalation methods, primarily utilize passive diffusion to transport drugs into the systemic circulation. The absorption rates and effectiveness of these routes depend on the drug's physicochemical properties, as well as the patient's anatomical and pathophysiological state.

Lipophilic drugs that are stable at salivary pH (6) and exhibit minimal binding to the oral mucosa are absorbed more effectively via sublingual and buccal routes. A prominent example is sublingual nitroglycerin, which is absorbed and transported from the mouth's venous system into the superior vena cava, bypassing first-pass hepatic metabolism and rapidly reaching a failing heart.

Topically-applied drugs on the foot and palm exhibit slow absorption due to the presence of a thick stratum corneum. In contrast, medications applied to burned or injured skin demonstrate accelerated absorption, especially when occlusive dressings are used to retain moisture.

Intramuscular injections provide varied absorption rates depending on the injection site. The arms, with a rich blood supply, yield faster absorption than the thighs, while the buttocks register the slowest absorption rate.

FInally, gaseous and aerosol drugs administered via inhalation are rapidly absorbed due to the lung's extensive surface area and rich vascular network.This rapid absorption makes it ideal for emergency treatments, such as bronchodilators for asthma. Understanding these absorption mechanisms is essential for developing optimal drug delivery systems.