Key result
In a provoked rat model of hypokalemia, co-administration of ranitidine twice daily with furosemide and clarithromycin significantly prolonged the QTc interval by 55.3% compared to baseline.
Why the study?
Does ranitidine prolong the QTc interval in a hypokalemia-provoked rat heart model?
Does ranitidine prolong the QTc interval in a hypokalemia-provoked rat heart model?
Ranitidine significantly prolongs the QTc interval in a provoked rat model with hypokalemia, highlighting potential arrhythmogenic risks under specific conditions.
Potential QTc interaction risk in hypokalemia; leaves open translation from rat model to humans.
Drugs with low arrhythmogenic tendencies fail to overcome the threshold to prolong QT interval and are ruled as safe. However, at provoked conditions these drugs might have the possibility to precipitate arrhythmia. Although small yet QT prolongation capability of such drugs must be investigated. The threshold required to prolong QT was attenuated using chronic dose of furosemide and clarithromycin. Once attenuated, QT prolongation capability of ranitidine was explored. Furosemide 10mg.kg - IP on co-administration with Clarithromycin 70mg.kg - orally for seven day manifested QTc interval at par with that of self-control group. A significant drop in serum potassium level was observed. In test groups, Furosemide 10mg.kg - + Clarithromycin 70 mg.kg - & Ranitidine 25 mg.kg -1 (once daily) and Furosemide 10mg.kg - + Clarithromycin 70 mg.kg - & Ranitidine 25 mg.kg -1 (Twice daily) the QTc prolongation compared to self control group was +28.0 % and +55.3 %, respectively. In the later group, the QT interval was observed to increase more than half the RR interval on ECG, a clinical indicator of cardiac emergency. Marked change in serum potassium level was also observed in the test groups. When Ranitidine alone was administered twice daily for seven days, no significant change in QTc interval was observed. Attenuation of the QT interval prolongation threshold exacerbates slightest QT prolongation tendencies and hence determine arrhythmogenic tendency of test drug. This model may be implied in the assessment of cardio-safety of drugs.
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Karmakar et al. (2017) studied Drug-induced QT prolongation in hypokalemia (n=24). Ranitidine vs. Self-control and Furosemide + Clarithromycin alone was evaluated on QTc interval prolongation (+55.3% increase, p=<0.05). In a provoked rat model of hypokalemia, co-administration of ranitidine twice daily with furosemide and clarithromycin significantly prolonged the QTc interval by 55.3% compared to baseline.
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