Pharmacokinetics of midazolam in the aged

Smith M.T., Heazlewood V., Eadie M.J., Brophy T.O. and Tyrer J.H. (1984) Pharmacokinetics of midazolam in the aged. European Journal of Clinical Pharmacology, 26 3: 381-388. doi:10.1007/BF00548771

Author Smith M.T.
Heazlewood V.
Eadie M.J.
Brophy T.O.
Tyrer J.H.
Title Pharmacokinetics of midazolam in the aged
Journal name European Journal of Clinical Pharmacology   Check publisher's open access policy
ISSN 0031-6970
Publication date 1984
Sub-type Article (original research)
DOI 10.1007/BF00548771
Volume 26
Issue 3
Start page 381
End page 388
Total pages 8
Publisher Springer-Verlag
Subject 3000 Pharmacology, Toxicology and Pharmaceutics
2736 Pharmacology (medical)
Abstract The pharmacokinetics of midazolam, an imidazo-benzodiazepine derivative, have been studied in 13 subjects over the age of 60 years who received the drug intravenously (0.07 mg kg-1) as an induction agent for endoscopy. Two to three days later, 6 of these subjects received 5 mg of midazolam intramuscularly, and another 6 of the subjects received 10 mg of the drug orally. The plasma concentration-time curves were again studied pharmacokinetically. After intravenous dosing, the mean (± SD) elimination half-life (2.14±1.24 h) showed a statistically significant trend to increase with age in the subjects older than 60 years. While the mean (± SD) clearance value (0.30±0.19 l kg-1h-1) tended to fall with age in the elderly subjects, this trend was not statistically significant. Apparent volume of distribution did not appear to be related to advancing age beyond 60 years, and this parameter (mean ± SD) did not differ to a statistically significant extent between the aged subjects (0.77±0.47 l kg-1) and the young subjects studied previously (1.09±0.58 l kg-1). Atropine premedication did not appear to alter the dispositional parameters of the intravenously administered drug. Intramuscularly administered midazolam was absorbed rapidly. Bioavailability appeared incomplete (F=0.59±0.15, mean ± SD), possibly due to saturable elimination of the drug at the higher plasma levels which were obtained after intravenous midazolam. Oral bioavailability, relative to intravenous, was 0.34±0.17, (mean ± SD), with an appreciable but variable lag time (0.74±0.40 h, mean ± SD). Orally, in the dose used, the drug was an inefficient hypnotic with four of the six subjects failing to attain the plasma drug level of 44-50 μg l-1, which appeared to be the approximate threshold for sleep. It is impossible to know whether this failure represents an age related effect on drug absorption, or is a consequence of the upper alimentary tract abnormalities for which the endoscopies were done.
Keyword aged patients
hypnotic drug
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import
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Citation counts: TR Web of Science Citation Count  Cited 37 times in Thomson Reuters Web of Science Article | Citations
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