Absorption | ↓ Absorption | Perfusion abnormalities Decreased GI motility Altered gastric pH Bowel wall edema Drug–nutrient interactions | Enteral, intramuscular, or subcutaneous drugs Itraconazole (capsules need an acidic medium for absorption), phenytoin (significant drug–nutrient interactions), subcutaneous enoxaparin (incompletely absorbed in the setting of vasopressors and edema) |
Distribution | ↑ Vd | Large-volume resuscitation Capillary leak syndrome Ascites Mechanical ventilation | Hydrophilic drugs Aminoglycosides, beta-lactams, daptomycin, hydromorphone, morphine, vancomycin |
Hypoalbuminemia | Albumin-bound drugs Amiodarone, ceftriaxone, midazolam, morphine, phenytoin, propofol, valproic acid, warfarin |
Extracorporeal circuits with expansive surface area (ECMO) | Lipophilic drugs Diazepam, fentanyl, fluoroquinolones, macrolides, midazolam, propofol |
↓ Vd | Decreased α1-acid glycoprotein | Drugs bound to α1-acid glycoprotein Azithromycin, carvedilol, fentanyl, lidocaine, olanzapine, phenobarbital |
Metabolism | ↑ Metabolism | Hepatic enzyme induction Augmented hepatic blood flow | Flow-dependent drugs (hepatic extraction ratio >0.7) Propofol, midazolam, morphine, metoprolol |
↓ Metabolism | Hepatic enzyme inhibition Decreased hepatic blood flow | Flow-independent drugs (hepatic extraction ratio <0.3) Warfarin, diazepam, phenytoin |
Excretion | ↑ Clearance | Augmented renal clearance Extracorporeal removal | Renally eliminated medications Beta-lactam antibiotics, vancomycin, enoxaparin, gabapentin, levetiracetam |
↓ Clearance | Acute kidney injury | Nephrotoxic medications Aminoglycosides, NSAIDs, antivirals, contrast |