Since the concentrations of PHC138 after SL administration are substantially higher than those found after oral administration, it is likely that this drug undergoes substantial first-pass metabolism. It is unlikely that poor absorption would be the cause for the difference, since a drug possessing physicochemical characteristics leading to poor oral absorption would be unlikely to be well absorbed by the SL route. If this drug does undergo first-pass metabolism, the metabolite concentrations after oral administration are going to be much higher than those following SL administration, since the latter avoids the first-pass effect. Hence, if the metabolite were the species displaying the pharmacologic activity, oral administration would result in a greater intensity and longer duration of pharmacologic effect than SL administration. The most plausible explanation for this observation is that PHC138 is a high first-pass drug whose activity resides in a metabolite.

Can you come up with another plausible explanation?

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