Which statement about 1-hydroxymidazolam is true?

Which statement about 1-hydroxymidazolam is true?

• A. Half as potent and rapidly conjugated to an inactive compound; renal failure will prolong the effect
• B. More potent than midazolam
• C. Not conjugated and remains active
• D. Inactive and not conjugated

Answer: (A)

Midazolam is metabolized in the liver to 1-hydroxymidazolam, an active metabolite with about half the potency of the parent drug. This metabolite is then rapidly conjugated to a glucuronide, which is pharmacologically inactive, and excreted by the kidneys. Because the metabolite still contributes to the overall effect but is cleared relatively slowly in renal impairment, renal failure prolongs the drug’s action. That combination—the metabolite being less potent than midazolam yet still active, and its rapid inactivation followed by slower renal clearance—explains why the statement is true. It is not correct that the metabolite is more potent, not conjugated and active, or simply inactive and not conjugated.

Midazolam is metabolized in the liver to 1-hydroxymidazolam, an active metabolite with about half the potency of the parent drug. This metabolite is then rapidly conjugated to a glucuronide, which is pharmacologically inactive, and excreted by the kidneys. Because the metabolite still contributes to the overall effect but is cleared relatively slowly in renal impairment, renal failure prolongs the drug’s action. That combination—the metabolite being less potent than midazolam yet still active, and its rapid inactivation followed by slower renal clearance—explains why the statement is true. It is not correct that the metabolite is more potent, not conjugated and active, or simply inactive and not conjugated.