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Editor,—There seem to be several possible problems with the recent paper by Oneta and colleagues (Gut1998;43:612–619). Firstly, blood ethanol concentrations said to result from an ethanol dosage of 0.225 g/kg were in the range of 0.2–0.3 mg/100 ml (figs 3–6 of Onetaet al's paper). These values are about 1% of the expected blood concentration for this dosage; presumably there was a 100-fold error in the labelling of the vertical axes of these four figures. Secondly, differences in the area under the curve were used to assess first pass metabolism when it has been repeatedly pointed out that this technique cannot be used when there is saturation of metabolism, as is the case with the ethanol dosage given. The authors irrationally justify their use of this inaccurate methodology by indicating that there may be problems with other methods. Furthermore, an appreciable fraction of the difference in the area under the curve seen with intravenous versus oral administration of ethanol seems to be attributable to incomplete distribution of the more rapidly delivered intravenous ethanol rather than a difference in metabolism. Finally, the authors found a positive correlation between first pass metabolism and gastric alcohol dehydrogenase (ADH) activity, which just missed reaching statistical significance (p=0.057 in antral biopsy samples). This positive correlation seems to be almost totally accounted for by the values of two subjects who had very high negative first pass metabolisms of −25% and −50%, respectively. Because, of course, there cannot be negative first pass metabolism, the values of these two subjects are suspect.
Editor,—We appreciate Furne and Levitt's comments on our paper and the error they noticed in figures 3–6. The concentrations on the vertical axes should indeed be 100-fold higher than published; they should read 20 mg/100 ml instead of 0.2 mg/100 ml. We regret this mislabelling; however, neither first pass metabolism of ethanol (given in percentages) nor its modulation by changes in gastric emptying are affected by this.
Differences in the area under the ethanol concentration time curves have been used previously to describe first pass metabolism of ethanol and give reliable approximations, although we are aware that this measurement has some disadvantages. Others have also used these differences,1-1 1-2 as mentioned in the discussion of our paper and which need not be repeated here. Ethanol was given intravenously over 30 minutes which allows some time for distribution. However, it is true that the input rate of ethanol affects its bioavailability and the area under the ethanol concentration time curve. If the input rate of ethanol through the different administration rates is similar—for example, comparable time profiles, the area under the curve method should still be valid.1-3
We did not find a significant positive correlation between first pass metabolism and gastric ADH activity as discussed in the results section of our paper, and it was emphasised in the discussion that such a correlation could not be confirmed. Thus, it did not seem necessary to exclude the two (statistically questionable) subjects with negative first pass metabolism in order to show that there was no correlation. Furthermore, it was not the purpose of this paper to give evidence for such a correlation. In contrast, changes in gastric emptying time may explain changes in first pass metabolism.
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