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British Journal of Anaesthesia, 1993, Vol. 70, No. 3 286-292
© 1993 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

PHARMACOKINETICS OF FLUMAZENIL AND MIDAZOLAM

R. D. M. JONES, F.A.N.Z.C.A., F.R.C.ANAES.*, K. CHAN, PH.D., F.R.PHARM.S., F.I.BIOL., F.C.P., F.A.C.B., C. J. ROULSON, F.R.C.ANAES, A. G. BROWN, F.R.C.ANAES, I. D. SMITH, F.R.C.ANAES. and G. H. MYA, F.R.C.S

Department of Anaesthesiology University of Hong Kong Hong Kong
Department of Pharmacology University of Hong Kong Hong Kong
Department of Surgery University of Hong Kong Hong Kong

*Address for correspondence: Department of Anaesthesiology, University of Hong Kong, Room 415, Block K, Queen Mary Hospital, Hong Kong.

.We have studied simultaneously the pharmaco-kinetics of flumazenil and midazolam in 12 healthy Chinese children, aged 5–9 yr, undergoing circumcision. Two hours before operation each patient received midazolam 0.5 mg kg-1 orally for pre-medication and 0.5 mg kg-1 i. v. during induction. Six minutes after cessation of anaesthesia, a bolus of flumazenil 10 ng kg-1 was given i. v., followed by an infusion of flumazenil at 5 fig kg-1 min-1 which was maintained until the child could identify himself. Midazolam data were consistent with a three-compartment model with a mean (SD) elimination half-life of 107 (30) min, total body clearance of 15.4 (3.2) ml min-1 kg7 and apparent volume of distribution at steady state of 1.9 (0.6) litre kg-1. Flumazenil data were best interpreted by a mono-exponential function, with a mean terminal elimination half-life of 35.3 (13.8) min, a total plasma clearance of 20.6 (6.9) ml minkg-1 and apparent volume of distribution at steady state of 1.0 (0.2) litre kg-1. No unchange midazolam was detected in the 24-h urine sample, but 5.8–13.8% of the flumazenil dose was recovered unchanged. At the time of self identification, 4.5 (1.4) min after flumazenil administration, the mean plasma concentrations of midazolam and flumazenil were 163.1 (43.7) and 29.9 (16.1) ngmt1, respectively. (Br. J. Anaesth. 1993; 70: 286–292)


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