Comparison of dissolution profile and plasma concentration-time profile of the thalidomide formulations made by Japanese, Mexican and British companies

Yukiyoshi Fujita, Koujirou Yamamoto, Tohru Aomori, Hirokazu Murakami, Ryuya Horiuchi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Thalidomide is an important advance in the treatment of multiple myeloma. In Japan thalidomide is now on the approval step for the treatment of multiple myeloma. The drug has some bothersome side effects such as defect of organogenesis, neuropathy, constipation and fatigue, but is likely more effective than standard chemotherapy and is changing multiple myeloma treatment. At this moment, Japanese patients must import the thalidomide preparations from Mexico, Britain and elsewhere, but after approval, they patients will be able to get the new Japanese thalidomide capsules. In order to determine appropriate amounts of Japanese thalidomide capsules in the treatment of multiple myeloma, we compared the dissolution profile and plasma thalidomide concentrations of Japanese and British capsules and Mexican tablets. The dissolution test was performed according to the Japanese and the United States Pharmacopoeia. The pharmacokinetic data for Japanese capsules were obtained from the clinical trial in Japanese subjects and compared with those data published for other formulations. The dissolution rate of the Japanese capsule was the fastest, followed by British and Mexican formulations. The pharmacokinetic profiles of Japanese and British capsules were similar, while the 100 mg Japanese thalidomide capsule demonstrated a 1.6-fold higher maximum plasma concentration than the 200 mg Mexican thalidomide tablet (1.7 vs. 1.1 μg/ml), greatly shortened tmax (4.5 vs. 6.2 h), and the apparent half life was only one-third of the Mexican tablet (4.8 vs. 13.5 h). A comparison of the dissolution and the pharmacokinetic absorption profiles demonstrated a rank-order correlation. Physicians and pharmacists should be aware of the probable alteration in plasma thalidomide concentration when switching to the Japanese capsule, especially from the Mexican tablet, and should monitor clinical response carefully.

Original languageEnglish
Pages (from-to)1449-1457
Number of pages9
JournalYakugaku Zasshi
Volume128
Issue number10
DOIs
Publication statusPublished - 2008 Oct 1

    Fingerprint

Keywords

  • Adverse effect
  • Bioequivalence
  • Dissolution test
  • Pharmacokinetics
  • Thalidomide

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this