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

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

Laboratory animals (2013-04-09)
M Katayama, P Jiamsripong, A E Bukatina, T R Lombari, E M McMahon, N M Gades, M Belohlavek
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.

MATERIALS
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Product Description

Supelco
Pentobarbital solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®