Phenobarbital Pharmacokinetics, Metabolism, and Clinical Implications

Respiratory Effects

• Phenobarbital suppresses the medullary respiratory center, leading to respiratory depression by reducing sensitivity to carbon dioxide. 1

Pharmacokinetic Parameters

• In adult patients, phenobarbital has an elimination half‑life of approximately 80–120 hours, reflecting its long‑acting nature. 1

Renal Elimination

• About 20–25 % of an administered dose of phenobarbital is excreted unchanged in the urine, allowing enhanced clearance through urinary alkalinization strategies. 1

Hepatic Enzyme Induction

• Phenobarbital induces cytochrome P450 enzymes, thereby increasing the metabolic clearance of co‑administered drugs that are CYP substrates. 1
• The drug is primarily metabolized by CYP2C9, with minor contributions from CYP2C19 and CYP2E1, and it exhibits auto‑induction that can lead to tolerance with chronic therapy. 1

Tolerance and Toxicity

• Tolerance develops to the sedative‑hypnotic effects of phenobarbital, but tolerance does not develop to lethal serum concentrations that cause respiratory failure, so life‑threatening toxicity can still occur despite chronic use. 1