The pharmacokinetics of midazolam and its metabolites were studied in 17 patients on mechanical ventilation in a general intensive care unit who were receiving a continuous intravenous infusion of midazolam, adjusted according to the level of induced sedation. Three patients were studied twice. Serum midazolam and alpha-hydroxymidazolamglucuronide levels were determined during and after infusion. The sedation level was scored on a four-point scale. Half of the observed patients were still drowsy or asleep 10 hours after termination of midazolam infusion. In only one patient was midazolam serum elimination half-life less than 2 hours and in six patients the half-life was greater than 10 hours. A wide range of midazolam serum levels was associated with adequate sedation, and similarly the midazolam levels at the moment of awakening were highly variable. The serum concentration ratio of midazolam/alpha-hydroxymidazolamglucuronide at the end of the infusion varied from 0.03 to 15.6. Renal function could account for only a part of this variation.
The pharmacokinetics of methotrexate and its 7-hydroxy metabolite were studied in a patient undergoing continuous ambulatory peritoneal dialysis. A biphasic plasma-disappearance pattern of methotrexate was observed, with half-lives of 3.5 and 29 hours. The 7-hydroxy metabolite accumulated and showed a very slow rate of elimination, with an estimated final elimination half-life of over 120 hours. The mean peritoneal clearance rate of methotrexate was 0.13 l/h (range 0.05-0.20 l/h), dwell times significantly influenced the clearance rate. Strict monitoring of the methotrexate level, even after low doses, is necessary in continuous ambulatory peritoneal dialysis patients, to prevent serious bone marrow toxicity.
Vol. 9 -I987 Pharmaceutisch Weekblad Scienttfic Edition officinale L. species complex and S. asperum Lepech. Part n. Phytosterols and triterpe.noids. Plant Syst Evol z983;I43:285-92. Wichers H J, Ten Kate J, Buys CHCM, Huizing HJ. A simple and rapid procedure to obtain nucleated proto-z87 plasts from plant material. Cytologia I984;49: xo3-9. Huizing H J, R6der E, Wiedenfeld H. Die '~C-NMR-Daten des Pyrrolizidine-Alkaloids Echimidin. Arch Pharm (Weinheim) *985;3*8:476-7. clinical pharmacological meeting Organized by the
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.