title: Dose escalation pharmacokinetics of intranasal scopolamine gel formulation.
abstract: Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing. We examined pharmacokinetics of 0.1, 0.2, and 0.4 mg doses of the Investigational New Drug formulation of intranasal scopolamine gel (INSCOP) in 12 healthy subjects using a randomized, double-blind cross-over study design. Subjects received one squirt of 0.1 g of gel containing either 0.1 mg or 0.2 mg/0.1 mL scopolamine or placebo in each nostril. Serial blood samples and total urine voids were collected after dosing and drug concentrations were determined using a modified LC-MS-MS method. Results indicate dose-linear pharmacokinetics of scopolamine with linear increases in Cmax and AUC within the dose range tested. Plasma drug concentrations were significantly lower in females than in males after administration of 0.4 dose. All three doses were well tolerated with no unexpected or serious adverse side effects reported. These results suggest that intranasal scopolamine gel formulation (INSCOP) offers a fast, reliable, and safe alternative for the treatment of motion sickness.
authors.affiliation: University of Houston Houston, College of Pharmacy, Houston, TX, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.forename: Jason L
authors.initials: JL
authors.lastname: Boyd
authors.forename: Vernie
authors.initials: V
authors.lastname: Daniels
authors.forename: Zuwei
authors.initials: Z
authors.lastname: Wang
authors.forename: Diana S-L
authors.initials: DS
authors.lastname: Chow
authors.forename: Lakshmi
authors.initials: L
authors.lastname: Putcha
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000932:Antiemetics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D005782:Gels; D006801:Humans; D008297:Male; D008875:Middle Aged; D012601:Scopolamine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D055815:Young Adult
chemical_list: D000932:Antiemetics; D005782:Gels; D012601:Scopolamine
keywords: dose escalation; intranasal; pharmacokinetics; scopolamine