Single Plasma Concentrations of 1′-Hydroxymidazolam or the Ratio of 1′-Hydroxymidazolam: Midazolam Do Not Predict Midazolam Clearance in Healthy Subjects

The 30‐minute ratio of 1′‐hydroxymidazolam: midazolam plasma concentrations has been used as a measure of midazolam clearance in liver transplant patients. This study determined if a single concentration of 1′‐hydroxymidazolam or the ratio of 1′‐hydroxymidazolam: midazolam could be used to predict m...

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Bibliographic Details
Published in:Journal of clinical pharmacology 2002-10, Vol.42 (10), p.1079-1082
Main Authors: Rogers, Janyce F., Nafziger, Anne N., Kashuba, Angela D. M., Streetman, Daniel S., Rocci Jr, Mario L., Choo, Edna F., Wilkinson, Grant R., Bertino Jr, Joseph S.
Format: Article
Language:English
Subjects:
Adult
Aged
Area Under Curve
Biological and medical sciences
Female
Humans
Hypnotics and Sedatives - blood
Hypnotics and Sedatives - pharmacokinetics
Hypnotics. Sedatives
Injections, Intravenous
Male
Medical sciences
Metabolic Clearance Rate
Midazolam - analogs & derivatives
Midazolam - blood
Midazolam - metabolism
Midazolam - pharmacokinetics
Multicenter Studies as Topic
Neuropharmacology
Pharmacology. Drug treatments
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
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Summary:The 30‐minute ratio of 1′‐hydroxymidazolam: midazolam plasma concentrations has been used as a measure of midazolam clearance in liver transplant patients. This study determined if a single concentration of 1′‐hydroxymidazolam or the ratio of 1′‐hydroxymidazolam: midazolam could be used to predict midazolam clearance in healthy subjects. Plasma midazolam and 1′‐hydroxymidazolam concentrations from three previous studies were used for analyses. Data obtained predose and at 5,30, 60,120,240, 300, and 360 minutes following intravenous doses of midazolam in 61 adults were divided and used to derive and validate equations to predict midazolam clearance. Equations were derived using linear regression and then validated by comparing predicted to observed clearance. Only one equation was related to midazolam clearance as a function of 1′‐hydroxymidazolam, but it did not predict midazolam clearance (r = 0.29, p = 0.31). Single sampling of 1′‐hydroxymidazolam or 1′‐hydroxymidazolam: midazolam plasma concentrations cannot be used to predict midazolam clearance in healthy adults.
ISSN:0091-2700
1552-4604
DOI:10.1177/009127002237986