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, Naomi M Gades, Marek Belohlavek

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 2013

Fingerprint

Lopinavir
Myocardial Reperfusion
myocardial ischemia
Myocardial Ischemia
Sprague Dawley Rats
rats
dosage
drugs
Serum
Pharmaceutical Preparations
Ritonavir
therapeutics
ischemia
pharmacokinetics
Reperfusion
Mammals
mouth
Ischemia
Animal Models
Pharmacokinetics

Keywords

  • Animal model
  • Lopinavir
  • Pharmacokinetics

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

Cite this

Optimized administration regimen of lopinavir for a myocardial ischaemia reperfusion study in Sprague-Dawley rats. / Katayama, M.; Jiamsripong, P.; Bukatina, A. E.; Lombari, T. R.; McMahon, E. M.; Gades, Naomi M; Belohlavek, Marek.

In: Laboratory Animals, Vol. 47, No. 2, 04.2013, p. 122-126.

Research output: Contribution to journalArticle

Katayama, M. ; Jiamsripong, P. ; Bukatina, A. E. ; Lombari, T. R. ; McMahon, E. M. ; Gades, Naomi M ; Belohlavek, Marek. / Optimized administration regimen of lopinavir for a myocardial ischaemia reperfusion study in Sprague-Dawley rats. In: Laboratory Animals. 2013 ; Vol. 47, No. 2. pp. 122-126.
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