Scopolamine

The pharmacokinetics of scopolamine differ substantially between different dosage routes. Oral administration of 0.5 mg scopolamine in healthy volunteers produced a C_max of 0.54 ± 0.1 ng/mL, a t_max of 23.5 ± 8.2 min, and an AUC of 50.8 ± 1.76 ng\*min/mL; the absolute bioavailability is low at 13 ± 1%, presumably because of first-pass metabolism.^A228758 By comparison, IV infusion of 0.5 mg scopolamine over 15 minutes resulted in a C_max of 5.00 ± 0.43 ng/mL, a t_max of 5.0 min, and an AUC of 369.4 ± 2.2 ng\*min/mL.^A228758 Other dose forms have also been tested. Subcutaneous administration of 0.4 mg scopolamine resulted in a C_max of 3.27 ng/mL, a t_max of 14.6 min, and an AUC of 158.2 ng\*min/mL. Intramuscular administration of 0.5 scopolamine resulted in a C_max of 0.96 ± 0.17 ng/mL, a t_max of 18.5 ± 4.7 min, and an AUC of 81.3 ± 11.2 ng\*min/mL. Absorption following intranasal administration was found to be rapid, whereby 0.4 mg of scopolamine resulted in a C_max of 1.68 ± 0.23 ng/mL, a t_max of 2.2 ± 3 min, and an AUC of 167 ± 20 ng\*min/mL; intranasal scopolamine also had a higher bioavailability than that of oral scopolamine at 83 ± 10%.^A228758 Due to dose-dependent adverse effects, the transdermal patch was developed to obtain therapeutic plasma concentrations over a longer period of time. Following patch application, scopolamine becomes detectable within four hours and reaches a peak concentration (t_max) within 24 hours. The average plasma concentration is 87 pg/mL, and the total levels of free and conjugated scopolamine reach 354 pg/mL.^L31578