Key result
High-dose oseltamivir lowers blood pressure and heart rate while prolonging PR and QRS in microminipigs.
Why the study?
Electropharmacological characteristics of microminipigs under halothane-anesthesia using oseltamivir, which blocks multiple ion channels, were not previously characterized.
Does oseltamivir alter electropharmacological characteristics in microminipigs?
Does oseltamivir alter electropharmacological characteristics in microminipigs?
Oseltamivir suppresses sinus automaticity and conduction while shortening repolarization in microminipigs, demonstrating their high sensitivity for Na+ and Ca2+ channel inhibition compared to beagle dogs.
Oseltamivir cardiac effects in microminipigs highlight model sensitivity differences; leaves open optimal preclinical species and human translation.
We analyzed electropharmacological characteristics of microminipigs under halothane-anesthesia using anti-influenza virus drug oseltamivir, which has been known to possess multi-channel blocking properties, including Na + , Ca 2+ and K + channels (n = 4).Oseltamivir in doses of 0.3, 3 and 30 mg/kg was intravenously infused over 10 min with an interval of 20 min, which provided peak plasma concentrations 1.4, 7.4 and 125.5 μg/mL, respectively.The low dose did not alter any of the cardiovascular variables.The middle dose decreased the heart rate at 30 min after the start of the infusion.The high dose transiently returned the heart rate toward the baseline for 10-15 min, but decreased it for 20-60 min; decreased the mean blood pressure for 5-60 min; prolonged the PR interval for 10-60 min, and the QRS width for 10-20 min; but shortened the QT interval for 10-30 min, and the QTc for 5-60 min.Thus, oseltamivir can suppress the sinus automaticity, and atrioventricular nodal and intraventricular conduction; and decrease the mean blood pressure, extents of which were greater in microminipigs than in beagle dogs in our previous observation in spite of similar plasma concentrations, reflecting higher sensitivity of microminipigs for Na + and Ca 2+ channel inhibition than that of beagle dogs.In contrast to beagle dogs, oseltamivir shortened the repolarization period in microminipigs, indicating that oseltamivir can more potently inhibit the inward currents than the outward ones in the hearts of microminipigs.This information may help improve utilizatione of microminipigs as a laboratory animal.
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Lubna et al. (2018) studied Healthy (animal model characterization) (n=4). Oseltamivir vs. Pre-drug baseline was evaluated on Changes in cardiovascular variables (heart rate, mean blood pressure, PR interval, QRS width, QT interval, QTc). High-dose oseltamivir (30 mg/kg) in microminipigs decreased heart rate and blood pressure, prolonged PR and QRS, but shortened QT and QTc, indicating higher sensitivity than beagle dogs.
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