Drug administration refers to the process of delivering pharmaceutical agents into the body through various routes, after which the body processes these drugs through a sequence of events collectively known as ADME.Absorption, Distribution, Metabolism, and Excretion. Understanding these processes is fundamental to pharmacy practice, as they determine a drug’s efficacy, safety, and appropriate dosing regimens.
Drug Administration Routes
The route of administration critically influences how rapidly and completely a drug reaches systemic circulation. Routes are broadly categorized as enteral (through the gastrointestinal tract) or parenteral (by injection).Enteral Routes include oral administration (tablets, capsules, liquids)—the most convenient and commonly used method—as well as sublingual and buccal administration, where drugs dissolve under the tongue or in the cheek, bypassing hepatic first-pass metabolism. Rectal administration via suppositories is also enteral.Parenteral Routes provide more direct access to systemic circulation. Intravenous (IV) administration delivers drug directly into the bloodstream, achieving 100% bioavailability. Intramuscular (IM) and subcutaneous (SC) injections provide intermediate absorption rates depending on blood flow to the injection site and drug solubility. Intrathecal administration delivers drugs around the spinal cord for cerebrospinal fluid access.
Alternative Routes include inhalation via the lungs (for local or systemic effects), topical application to skin, vaginal, and ophthalmic routes. For orally administered drugs, this process involves crossing the gastrointestinal tract barrier and is influenced by multiple factors.Factors Affecting Oral Absorption include drug disintegration from the dosage form, dissolution of particles, chemical stability, resistance to enzymatic degradation, gastrointestinal tract motility and mixing, presence and type of food in the stomach, the ability to cross the GI wall, blood flow to the gastrointestinal tract, and gastric emptying time. Additionally, formulation design such as enteric coating or extended-release mechanisms significantly modulates absorption kinetics.
First-Pass Metabolism is a critical determinant of oral drug bioavailability. When drugs are absorbed from the gastrointestinal tract, they enter the hepatic portal vein and are transported directly to the liver before reaching systemic circulation. The liver contains abundant cytochrome P450 enzymes particularly CYP3A4—which metabolize many drugs extensively. This hepatic “first-pass” can dramatically reduce bioavailability. For example, the HIV protease inhibitor lopinavir has oral bioavailability of only 25% due to rapid CYP450-mediated metabolism.To overcome this limitation, clinicians may coadminister enzyme inhibitors (such as ritonavir) or employ alternative routes (sublingual, parenteral) that bypass hepatic metabolism.
Bioavailability (F) quantifies the fraction of an administered dose that reaches systemic circulation. IV administration achieves 100% bioavailability by definition.For other routes, bioavailability is calculated by comparing the area under the plasma concentration-time curve (AUC) to that of IV administration. A drug with 50% oral bioavailability requires twice the oral dose to achieve equivalent systemic exposure compared to an IV dose.
Drug Transport Mechanisms across cell membranes include passive diffusion through lipid membranes (governed by lipid solubility, concentration gradient, and drug surface area), diffusion through aqueous pores (limited to small, charged molecules), carrier-mediated transport (selective and saturable), ion channels, and pinocytosis (for large molecules
MBH/PS