Abstract
Purpose. The present study was conducted to evaluate theeffects of formulation pH and dose on nasal absorption of scopolaminehydrobromide, the single most effective drug available for the prevention ofnausea and vomiting induced by motion sickness.
Methods. Human subjects received scopolamine nasally at adose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected atdifferent time points, and plasma scopolamine concentrations were determinedby LC-MS/MS.
Results. Following administration of a 0.2 mg dose, theaverage Cmax values were found to be 262 ± 118, 419± 161, and 488 ± 331 pg/mL for pH 4.0, 7.0, and 9.0formulations, respectively. At the 0.4 mg dose the average Cmaxvalues were found to be 503 ± 199, 933 ± 449, and 1,308± 473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a0.2 mg dose, the AUC values were found to be 23,208 ± 6,824, 29,145± 9,225, and 25,721 ± 5,294 pg.min/mL for formulation pH 4.0,7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value wasfound to be high for pH 9.0 formulation (70,740 ± 29,381 pg.min/mL)as compared to those of pH 4.0 (59,573 ± 13,700 pg.min/mL) and pH 7.0(55,298 ± 17,305 pg.min/mL) formulations. Both the Cmaxand AUC values were almost doubled with doubling the dose. On the otherhand, the average Tmax values decreased linearly with a decreasein formulation pH at both doses. For example, at a 0.4 mg dose, the averageTmax values were 26.7 ± 5.8, 15.0 ± 10.0, and 8.8± 2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively.
Conclusions. Nasal absorption of scopolamine hydrobromidein human subjects increased substantially with increases in formulation pHand dose.
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Ahmed, S., Sileno, A.P., deMeireles, J.C. et al. Effects of pH and Dose on Nasal Absorption of Scopolamine Hydrobromide in Human Subjects. Pharm Res 17, 974–977 (2000). https://doi.org/10.1023/A:1007551927177
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DOI: https://doi.org/10.1023/A:1007551927177