Application of a sample pooling method for the accelerated assessment of the rate of uptake of drugs by the brain in rats

Kang Pil Kim, Sung Hoon Ahn, Jong Hyuk Sung, Tae Sung Koo, Myong Joo Byun, Dae Duk Kim, Chang Koo Shim, Suk Jae Chung

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The purpose of this study was to examine the feasibility of applying a sample pooling method to the accelerated estimation of the uptake clearance of drugs to the brain in rats. Brain uptake clearances (CLuptake) were estimated for five model compounds using the sample pooling method and an integration plot analysis. CLuptake was also evaluated for caffeine and theophylline by brain microdialysis. The parameters and throughput of the pooling method were compared with those of typically used standard methods. The correlation for CLuptake was statistically significant (P < 0.005) between the integration plot and the current method; the throughput of evaluation was 15-fold higher for the sample pooling method. A comparison of CLuptake values indicated that the three methods showed comparable results for caffeine while the CLuptake of theophylline using the proposed method was significantly different from those of the other methods. A kinetic analysis indicated that a compound with a slower CLuptake and longer half-life (e.g., theophylline) is more prone to error and that the lower limit of the CLuptake of 0.17 mL min-1 (g brain) -1 may be set so as to have an error less than 20% of the estimation. These results suggest that the sample pooling method is applicable for use in the accelerated estimation of the uptake clearance of compounds in the brain for which the value is greater than 0.17 mL min-1 (g brain) -1.

Original languageEnglish
Pages (from-to)837-846
Number of pages10
JournalJournal of Pharmacy and Pharmacology
Volume58
Issue number6
DOIs
Publication statusPublished - 2006 Jun

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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