Article date: February 1990
By: RJ Wills, KC Khoo, PP Soni, IH Patel, in Volume 29, Issue 2, pages 269-272
It has recently been shown by several investigators that the half‐life (t1/2) of midazolam is prolonged (greater than 7 h) in a small proportion of the population. One group has inferred that this subpopulation represents a group of slow metabolizers of midazolam to alpha‐OH‐midazolam. Others disagree and postulate that there is an increase in the volume of distribution (V) resulting in a prolonged t1/2. This controversy led us to report experience from 90 subjects and patients where t1/2, V, and clearance (CL) were determined by both model‐dependent and ‐independent pharmacokinetic analysis. We found a 5.6% (5 of 90) incidence of prolonged t1/2, similar to that previously reported. V was clearly increased without a decrease in CL in the five subjects with prolonged t1/2. Thus, the prolonged t1/2 is secondary to an increase in V and not a result of alterations in CL and metabolism.
DOI: 10.1111/j.1365-2125.1990.tb03633.x
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