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Increased volume of distribution prolongs midazolam half-life.
Wills, R J; Khoo, K C; Soni, P P; Patel, I H.
Afiliación
  • Wills RJ; Department of Drug Metabolism, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Br J Clin Pharmacol ; 29(2): 269-72, 1990 Feb.
Article en En | MEDLINE | ID: mdl-2306422
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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Midazolam Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Br J Clin Pharmacol Año: 1990 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Midazolam Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Br J Clin Pharmacol Año: 1990 Tipo del documento: Article Pais de publicación: Reino Unido