Scopolamine bioavailability in combined oral and transdermal delivery.

Author(s): Nachum Z, Shahal B, Shupak A, Spitzer O, Gonen A, Beiran I, Lavon H, Eynan M, Dachir S, Levy A.

Affiliation(s): Motion Sickness and Human Performance Laboratory, Israel Naval Medical Institute, IDF Medical Corps, Haifa, Israel.

Publication date & source: 2001, J Pharmacol Exp Ther. , 296(1):121-3

Transdermal therapeutic system scopolamine (TTS-S) is effective in preventing motion sickness for 72 h. However, by this route a prophylactic effect is obtained 6 to 8 h postapplication. By the oral route, scopolamine is effective within 0.5 h for a period of 6 h. To achieve safe as well as effective protection against seasickness during the first hours of a voyage until the TTS-S patch takes effect, the pharmacokinetics of scopolamine was investigated after patch application in combination with oral tablets, 0.6 mg, 0. 3 mg, or placebo. Subjects were 25 naval-crew volunteers, randomly divided into three groups: group 1 (n = 9), TTS-S patch + 0.6 mg of scopolamine per os (p.o.); group 2 (n = 8), TTS-S patch + 0.3 mg of scopolamine p.o.; and group 3 (n = 8), TTS-S patch + placebo tablet. Blood samples were collected before treatment and 0.5, 1, 1.5, 2.5, 3.5, 6, 8, and 22 h post-treatment, and were analyzed for scopolamine levels using radioreceptor assay. Significantly higher plasma scopolamine levels were found in group 1 at 0.5, 1, 1.5, and 2.5 h, and in group 2 at 1 and 1.5 h post-treatment, compared with group 3. Thereafter, plasma levels did not differ significantly between the groups. In all subjects of group 1 and seven subjects (88%) of group 2, therapeutic levels (>50 pg/ml) were measured during the first 2.5 h, compared with only two subjects (25%) of group 3 (P < 0.05). Heart rate, blood pressure, visual accommodation, performance test results, and subjective complaints of adverse effects did not differ significantly. The combination of transdermal and oral scopolamine (0.3 or 0.6 mg) provides the required plasma levels to prevent seasickness, starting as early as 0.5 h post-treatment, with no significant adverse effects.