Intranasal Pharmacokinetic Data for Triptans Such as Sumatriptan and Zolmitriptan Can Render Area Under the Curve (AUC) Predictions for the Oral Route: Strategy Development and Application

ABSTRACT

Limited pharmacokinetic sampling strategy may be useful for predicting the area under the curve (AUC) for triptans and may have clinical utility as a prospective tool for prediction. Using appropriate intranasal pharmacokinetic data, a C_max vs. AUC relationship was established by linear regression models for sumatriptan and zolmitriptan. The predictions of the AUC values were performed using published mean/median C_max data and appropriate regression lines. The quotient of observed and predicted values rendered fold-difference calculation. The mean absolute error (MAE), mean positive error (MPE), mean negative error (MNE), root mean square error (RMSE), correlation coefficient (r), and the goodness of the AUC fold prediction were used to evaluate the two triptans. Also, data from the mean concentration profiles at time points of 1 hour (sumatriptan) and 3 hours (zolmitriptan) were used for the AUC prediction. The C_max vs. AUC models displayed excellent correlation for both sumatriptan (r = .9997; P < .001) and zolmitriptan (r = .9999; P < .001). Irrespective of the two triptans, the majority of the predicted AUCs (83%–85%) were within 0.76–1.25-fold difference using the regression model. The prediction of AUC values for sumatriptan or zolmitriptan using the concentration data that reflected the T_max occurrence were in the proximity of the reported values. In summary, the C_max vs. AUC models exhibited strong correlations for sumatriptan and zolmitriptan. The usefulness of the prediction of the AUC values was established by a rigorous statistical approach.

KEYWORDS:

• Sumatriptan
• zolmitriptan
• pharmacokinetics
• intranasal
• linear regression