Similar rivastigmine pharmacokinetics and pharmacodynamics in Japanese and white healthy participants following the application of novel rivastigmine patch

J Clin Pharmacol. 2009 Apr;49(4):430-43. doi: 10.1177/0091270008330161. Epub 2009 Feb 26.

Abstract

The pharmacokinetics and pharmacodynamics of rivastigmine were compared in Japanese and white healthy participants who were given ascending single doses of the novel rivastigmine transdermal patch. Rivastigmine patch strengths were 4.6 mg/24 h (5 cm2, 9 mg rivastigmine loaded dose), 9.5 mg/24 h (10 cm2, 18 mg), and 13.3 mg/24 h (15 cm2, 27 mg) (per label) or 7.0 mg/24 h (7.5 cm2, 13.5 mg) as a fall-back dose. No relevant ethnic differences in the noncompartmental pharmacokinetics (parent and metabolite NAP226-90) and pharmacodynamics (plasma BuChE activity) of the rivastigmine patch were observed between Japanese and whites. However, drug exposure was slightly higher and inhibition of BuChE slightly more pronounced in Japanese participants than in whites, which was attributed to the lower body weight (ca. 11% less on average) of Japanese participants. Treatments were similarly well tolerated in both ethnic groups. In conclusion, no relevant ethnic differences in the intrinsic disposition or effects of rivastigmine delivered via transdermal route are expected between Japanese and white patients. The possible effect of body weight on drug exposure suggests that special attention should be paid to patients with very low body weight during up-titration.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous*
  • Adult
  • Asian People
  • Butyrylcholinesterase / blood
  • Cholinesterase Inhibitors / administration & dosage*
  • Cholinesterase Inhibitors / adverse effects
  • Cholinesterase Inhibitors / pharmacokinetics*
  • Drug Delivery Systems
  • Humans
  • Male
  • Phenylcarbamates / administration & dosage*
  • Phenylcarbamates / adverse effects
  • Phenylcarbamates / pharmacokinetics*
  • Rivastigmine
  • White People

Substances

  • Cholinesterase Inhibitors
  • Phenylcarbamates
  • Butyrylcholinesterase
  • Rivastigmine