Pharmacokinetics: Drug Absorption and Bioavailability
Concept Name
Drug Absorption
Genetic Loci
ABCB1 (7q21.12) encodes P‑glycoprotein (MDR1) – polymorphisms affect drug absorption and CNS penetration. SLC22A1 (6q25.3) encodes OCT1 for hepatic uptake of metformin.
Intracellular Cascade
Drugs cross membranes via passive diffusion (pH‑dependent for weak acids/bases), facilitated diffusion (SLC transporters), or active transport (ABC transporters). First‑pass metabolism by liver reduces oral bioavailability (F = fabs × fgut × fhep).
Required Cofactors
No specific cofactors; gastric pH (influenced by proton pump inhibitors) affects ionization and absorption of weak acids/bases.
Histology Stains
Enterocytes express various transporters; immunohistochemistry for P‑glycoprotein shows apical membrane localization in the intestine.
EM Findings
Microvilli on enterocytes increase surface area for absorption. Tight junctions (occludin, claudin) regulate paracellular transport.
Knockout Phenotype
Knockout of ABCB1 (Mdr1a) in mice leads to increased brain penetration of ivermectin, causing neurotoxicity (used as a model for drug‑drug interactions).
Specific Toxins
Grapefruit juice inhibits intestinal CYP3A4 and P‑glycoprotein, increasing oral bioavailability of many drugs (e.g., felodipine, cyclosporine). Rifampin induces CYP3A4 and P‑glycoprotein, decreasing drug levels.