Optimized administration regimen of lopinavir for a myocardial ischaemia reperfusion study in Sprague-Dawley rats

M. Katayama, P. Jiamsripong, A. E. Bukatina, T. R. Lombari, E. M. McMahon, N. M. Gades, M. Belohlavek

Research output: Contribution to journalArticle

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Abstract

Pharmacokinetics of drugs may differ between small and large mammals (including humans); therefore, drug testing in animal models must be carefully designed. Sprague-Dawley rats were used in cardiac experiments, during which the lopinavir concentration in serum had to match human therapeutic levels (4-10 μg/mL). Lopinavir was administered as a co-formulated drug of lopinavir and ritonavir. It was found that after a single administration of a standard human peroral dose (lopinavir 13.3 mg/kg of body weight), the serum concentration of lopinavir was only one-tenth of the target level. It remained below the minimum target level even after 10-fold the standard dose was administered. After initial pilot tests, a dose escalation study was conducted with oral doses 10- and 15-fold the standard clinical dose of lopinavir (i.e. 133 and 200 mg/kg, respectively). A second administration 2 h later effectively increased and maintained higher concentrations during the experimental ischaemia and reperfusion periods. A dose-dependent increase in serum concentration of the drug was observed. Thus, the target therapeutic serum level of lopinavir in the rats was achieved by administrating 10- to 15-fold the standard human dose twice, separated by a 2 h interval.

Original languageEnglish (US)
Pages (from-to)122-126
Number of pages5
JournalLaboratory Animals
Volume47
Issue number2
DOIs
StatePublished - Apr 1 2013

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Keywords

  • Animal model
  • Lopinavir
  • Pharmacokinetics

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

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