Which statement about midazolam metabolism is true?

• A. It does not cross the blood-brain barrier
• B. It is converted to an inactive metabolite
• C. It is primarily metabolized by CYP3A4 to an active metabolite called 1-hydroxymidazolam
• D. It is eliminated exclusively by the kidneys unchanged

Answer: (C)

Midazolam is a benzodiazepine that readily crosses the blood-brain barrier to produce sedation, so statement that it does not cross the barrier is incorrect. The drug is cleared mainly by the liver through metabolism by cytochrome P450 enzymes, especially CYP3A4. The principal metabolic step is hydroxylation to 1-hydroxymidazolam, which remains pharmacologically active and contributes to the overall sedative effect. This active metabolite is then further processed (glucuronidated) and excreted, rather than the parent drug being eliminated unchanged by the kidneys. So the correct idea is that midazolam is primarily metabolized by CYP3A4 to an active metabolite called 1-hydroxymidazolam.