Blood concentrations of midazolam in status epilepticus using an appropriate condition of HPLC.
BACKGROUND
The aim of the present study was to determine an index to evaluate the efficacy and safety of midazolam (MDZ) to treat status epilepticus (SE). An original system was therefore developed to measure blood concentrations of MDZ and 1-hydroxymidazolam (1-OHMDZ) as the main metabolite on high-performance liquid chromatography.


METHODS
This system was established through inspection of chromatograms, calibration curves and coefficient of correlations of MDZ. The clinical course of 11 SE patients, ranging from 4 months to 10 years of age, are described. These patients were treated with MDZ and measured at each blood concentration of MDZ. Moreover, patients were evaluated on cranial computed tomography and magnetic resonance imaging and video electroencephalogram (EEG), and it was determined that their seizures disappeared in accordance with the disappearance of convulsions and interictal EEG findings.


RESULTS
Reproducibility was good with this system. The standard curves of MDZ and 1-OHMDZ were almost straight, and the correlation coefficients of MDZ and 1-OHMDZ were r = 0.9999 and r = 0.9998, respectively. The convulsions in nine of 11 SE patients disappeared without side-effects and the blood concentrations of MDZ in all the patients were measured. The mean peak blood concentrations of MDZ and 1-OHMDZ were higher than those reported in other studies.


CONCLUSIONS
The clinical utility of this system has been demonstrated. An index to evaluate the efficacy and safety of MDZ is necessary, and MDZ blood concentrations measured on the present original precise measuring system could help in establishing a plan to successfully treat SE.
Iwasaki
Toshiyuki
T
Department of Pediatrics, Kitasato University School of Medicine, Kanagawa, Japan. tiwasaki@kitasatou.ac.jp
Nonoda
Yutaka
Y
Ishii
Masahiro
M
Osawa
Makiko
M
D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008874:Midazolam / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013226:Status Epilepticus / Q000188:drug therapy* / Q000378:metabolism
C040081:1-hydroxymethylmidazolam; D008874:Midazolam