Pharmacokinetic-pharmacodynamic analyses of antihypertensive drugs, nifedipine and propranolol, in spontaneously hypertensive rats to investigate characteristics of effect and side effects

Regulatory Toxicology and Pharmacology : RTP
Akiko KiriyamaKatsumi Iga

Abstract

To investigate the relationship between the pharmacokinetics (PK) and effects and/or side-effects of nifedipine and propranolol, simultaneous examination of their PK and pharmacodynamics (PD), namely blood pressure (BP), heart rate (HR), and QT interval (QT), were assessed in spontaneously hypertensive rats as a disease model. Drugs were infused intravenously for 30 min, then plasma PK and hemodynamic effects were monitored. After general two-compartmental analysis was applied to the plasma data, PD parameters were calculated by fitting the data to PK-PD models. After nifedipine administration, the maximal hypotensive effect appeared about 10 min after starting the infusion, then BP started to elevate although the plasma concentration increased, supposedly because of a negative feedback mechanism generated from the homeostatic mechanism. After propranolol administration, HR decreased by half, and this bradycardic effect was greater than that with nifedipine. Wide variation in QT was observed when the propranolol concentration exceeded 700 ng/mL. This variation may have been caused by arrhythmia. Prolongation of QT with propranolol was greater than that with nifedipine, and bradycardia was slower than the concentration increase ...Continue Reading

References

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Citations

Nov 4, 2017·International Journal of Molecular Sciences·Yi-Huang HsuehChien-Hui Wu
Mar 2, 2021·Colloids and Surfaces. B, Biointerfaces·Nikita AgrawalSanghamitra Chatterjee
Mar 3, 2021·The Journal of Pharmacology and Experimental Therapeutics·Mikael WallmanJohan Gabrielsson
Apr 6, 2021·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Jiaojiao YuLiandong Hu
Jul 16, 2019·Thérapie·Béatrice BouhanickPeggy Gandia

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