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Exploring the multiple effects of nifedipine and captopril administration in spontaneously hypertensive rats through pharmacokinetic-pharmacodynamic analyses.

التفاصيل البيبلوغرافية
العنوان: Exploring the multiple effects of nifedipine and captopril administration in spontaneously hypertensive rats through pharmacokinetic-pharmacodynamic analyses.
المؤلفون: Kiriyama A; Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyoto, Japan., Kimura S; Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyoto, Japan., Yamashita S; Department of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyoto, Japan.
المصدر: Pharmacology research & perspectives [Pharmacol Res Perspect] 2024 Aug; Vol. 12 (4), pp. e1249.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 101626369 Publication Model: Print Cited Medium: Internet ISSN: 2052-1707 (Electronic) Linking ISSN: 20521707 NLM ISO Abbreviation: Pharmacol Res Perspect Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Hoboken, NJ] : John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics, [2013]-
مواضيع طبية MeSH: Captopril*/pharmacokinetics , Captopril*/administration & dosage , Captopril*/pharmacology , Nifedipine*/pharmacokinetics , Nifedipine*/administration & dosage , Nifedipine*/pharmacology , Rats, Inbred SHR* , Antihypertensive Agents*/pharmacokinetics , Antihypertensive Agents*/administration & dosage , Antihypertensive Agents*/pharmacology , Blood Pressure*/drug effects , Hypertension*/drug therapy , Hypertension*/chemically induced , Heart Rate*/drug effects, Animals ; Male ; Rats ; Drug Interactions ; Half-Life ; Drug Therapy, Combination
مستخلص: This study assessed the pharmacokinetics (PKs) and pharmacodynamics (PDs) of two antihypertensive drugs, nifedipine and captopril, by exploring their main (blood pressure [BP]) and secondary effects (heart rate [HR] and QT interval [QT]) in spontaneously hypertensive rats. This study aimed to assess the relationship between PKs and PDs. Using these PD parameters, BP, HR, and QT during coadministration were estimated. The coadministration of nifedipine and captopril resulted in an increase in nifedipine's total body clearance (CL tot ) and a reduction in its mean residence time (MRT) with an increase in the terminal elimination half-life (t 1/2 ) and volume of distribution at steady state (V dss ) of captopril. However, no significant PK interactions were observed. During monotherapy, BP reduced rapidly following nifedipine infusion. Subsequently, despite the increase in nifedipine plasma concentration, BP recovered, likely because of homeostasis. Similar results were observed with coadministration. Subsequently, BP demonstrated a sustained reduction that was greater than or equal to the additive effect estimated from each PK. Captopril exhibited a minimal effect on HR, except for a transient increase observed immediately after starting infusion, consistent with observations during coadministration. Subsequently, the HR reduction was nearly equal to that calculated from the nifedipine PK. QT prolongation was more rapid with captopril than with nifedipine. Although QT prolongation during the initial 60 min of coadministration was approximately the sum of both effects, the recovery period to baseline QT was faster than that in the simulation.
(© 2024 The Author(s). Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)
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فهرسة مساهمة: Keywords: QT interval; blood pressure; captopril; heart rate; nifedipine; pharmacokinetic‐pharmacodynamic (PK‐PD) model; spontaneously hypertensive rat (SHR)
المشرفين على المادة: 9G64RSX1XD (Captopril)
I9ZF7L6G2L (Nifedipine)
0 (Antihypertensive Agents)
تواريخ الأحداث: Date Created: 20240717 Date Completed: 20240717 Latest Revision: 20240719
رمز التحديث: 20240719
مُعرف محوري في PubMed: PMC11253705
DOI: 10.1002/prp2.1249
PMID: 39017590
قاعدة البيانات: MEDLINE
الوصف
تدمد:2052-1707
DOI:10.1002/prp2.1249