Oral sumatriptan and almotriptan--delimiting the MAOI effect

(Headache 2012;52:765‐772) Objectives/Background.— (1) To investigate whether a parsimonious model for sumatriptan pharmacokinetics can apply to oral administration; (2) for a successful model, whether a monoamine oxidase A inhibitor (MAOI‐A) perturbs it; and (3) whether such a model is generalizable to oral almotriptan. These goals respond to statements in US product labeling. Methods.— Extension of a previous model for subcutaneous sumatriptan. Numerical solutions to 3 concurrent differential equations were found, with prospective criteria for model acceptance based upon comparison with clinically observed data. Results.— The model was successfully extended by inserting a time factor into the absorption phase. This extension was robust: it imitated clinical data for 3 oral sumatriptan dose sizes (both without and with a concomitant MAOI‐A) and also for oral almotriptan. Conclusion.— A model for oral sumatriptan pharmacokinetics can be found using the differential calculus, and it is generalizable to oral almotriptan. The model suggests that an MAOI‐A probably has greater effect on elimination kinetics than first‐pass metabolism, and that this interaction appears to be overstated in product labeling.