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Dockhorn et al reported a comparison of the effect of intravenous and oral montelukast and placebo on forced expiratory volume in one second (FEV1).1 They found the mean percentage change from baseline was significantly higher from 15 minutes to one hour with intravenous compared with oral montelukast, and suggested that this may be the result of more favourable interaction kinetics with the cysteinyl leukotriene receptor. The doses of montelukast chosen were based on an unpublished study which showed that the area under the plasma concentration time curve (AUC) for the 7 mg intravenous dose was comparable to the 10 mg oral dose. The time over which the AUC was measured was not stated by the authors, and all other aspects of the pharmacokinetics of these two formulations were not described. It is known that the Tmax of intravenous montelukast is within the first hour2 3 and that the Tmax of oral montelukast is at approximately three hours.2-4 Distribution of montelukast to the lung cysteinyl leukotriene receptors would therefore be expected to be more rapid with the intravenous formulation, causing a greater increase in FEV1 at the earlier time points. The authors do not appear to have considered this possibility. The faster onset of action of intravenous montelukast was well demonstrated in this study, but we feel that an important possible explanation for this finding was inadequately discussed.
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