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Abstract
Clomethiazole, a sedative-hypnotic and anticonvulsant drug, has been successfully
administered orally and intravenously, but in cases where either of these methods
presents complications, rectal administration may represent a practical alternative.
We sought to compare the single-dose pharmacokinetics and pharmacodynamics of clomethiazole
after oral and rectal administration. Ten healthy adult volunteers were given 600
mg clomethiazole edisylate (corresponding to 390 mg clomethiazole ase) in 2 capsules
as a single oral or rectal dose in a double-masked, doubledummy, crossover fashion.
Serum concentrations were measured up to 10 hours after administration using a specific
highperformance liquid chromatography method. Computerized reaction-time measurement
and visual analogue scales (VAS) were used to assess drug effects. Peak serum concentrations
were significantly higher after oral administration (mean ±SEM, oral 1.76 ± 0.47 (μg/mL
vs rectal 0.48 ± 0.14 μg/mL; P = 0.03) and appeared earlier (55 ± 12 vs 89 ± 11 min; P = 0.04). Area under the concentrationtime curve values were similar after administration
by both routes (oral 116 ±20.6 vs rectal 105 ± 36.0 μg·min/mL), with a relative rectal
bioavailability of 90% compared with oral administration. The objective pharmacodynamic
effects on reaction time (increase of 104 ± 26 vs 66 ± 22 ms, oral vs rectal) and
working speed (decrease of 132 ± 38 vs 97 ± 32 ms, oral vs rectal) were not significantly
different. Subjective pharmacodynamic effects, as measured on the VAS, were comparable
with both routes of administration. Clomethiazole was well tolerated, with a similar
adverse effect profile for both routes of administration. The effects of rectal dosing
of clomethiazole were similar to those of oral dosing but appeared to occur later.
Our results suggest that rectal administration of a single 600-mg Clomethiazole edisylate
dose bears no safety risk. Therefore, rectal administration could be considered when
neither oral nor parenteral administration is possible and a later onset of effect
is not critical.
Key words
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Article info
Publication history
Accepted:
February 11,
1999
Identification
Copyright
© 1999 Published by Elsevier Inc.
