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Pharmaceutics
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Pharmacokinetic and Pharmacodynamic Considerations for Drugs Used in the Treatment...
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Pharmacokinetic and Pharmacodynamic Considerations for Drugs Used in the Treatment of Cardiovascular Diseases

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmacokinetics and Pharmacodynamics".

Deadline for manuscript submissions: closed (20 January 2025) | Viewed by 3927

Special Issue Editors

Dr. Noriko Daneshtalab

E-Mail Website
Guest Editor
School of Pharmacy, Memorial University of Newfoundland and Labrador, St. John’s, NL A1B 3V6, Canada
Interests: pharmacokinetics; pharmacodynamics; pharmacology; stroke research; inflammation; imaging
Dr. Reza Tabrizchi

E-Mail Website
Guest Editor
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada
Interests: cardiovascular; pharmacology; physiology; arterial stiffness; cardiac; adrenergic receptor signaling

Special Issue Information

Dear Colleagues,

Current considerations in pharmacokinetics and pharmacodynamics for cardiovascular drugs include personalized medicine, drug–drug interactions, comorbidity considerations, and innovative drug delivery systems. These factors collectively contribute to optimizing treatment outcomes and patient safety in the management of cardiovascular diseases, which we would like to touch on this Special Issue of Pharmaceutics.

Pharmacokinetic and pharmacodynamic considerations play a crucial role in the effective treatment of cardiovascular diseases and several noteworthy considerations have emerged.

One current consideration in the field of pharmacokinetics is the potential for drug–drug interactions at different levels of ADME. In terms of pharmacodynamics, current considerations include investigating drugs that target specific pathways involved in cardiovascular disease, such as inflammation and thrombosis. Additionally, there is a growing interest in personalized medicine, which involves tailoring drug therapy to an individual's physiological characteristics such as age, gender, and renal and hepatic function, as well as genetic factors. Advancements in pharmacogenomics have highlighted the importance of genetic variations in drug response. Genetic testing can identify individuals at increased risk of adverse effects or non-response to certain cardiovascular medications, allowing for personalized treatment plans. The impact of comorbidities on pharmacokinetics and pharmacodynamics is also gaining attention. Conditions such as liver disease, renal impairment, and heart failure can significantly alter drug metabolism and distribution, requiring dose adjustments or alternative treatment strategies. Lastly, advancements in drug delivery systems, such as targeted drug delivery, have the potential to enhance drug efficacy, reduce dosing frequency, and improve patient compliance.

Dr. Noriko Daneshtalab
Dr. Reza Tabrizchi
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • pharmacokinetics
  • pharmacodynamics
  • cardiovascular diseases
  • drug-drug interaction
  • targeted drug delivery
  • pharmacogenomics
  • co-morbidity
  • personalized medicine

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Published Papers (2 papers)

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Research

14 pages, 2167 KiB  
Article
Effect of Staggered vs. Simultaneous Co-Administration of Bempedoic Acid on Pharmacokinetics of Pravastatin: Randomized, Cross-Over Clinical Trial in Healthy Volunteers
by Felicitas Stoll, Salvatore Amato, Max Sauter, Jürgen Burhenne, Johanna Weiss, Walter E. Haefeli and Antje Blank
Pharmaceutics 2025, 17(1), 60; https://doi.org/10.3390/pharmaceutics17010060 - 3 Jan 2025
Cited by 1 | Viewed by 1085
Abstract
Background/Objectives: Bempedoic acid (BA) is a novel cholesterol-lowering agent with proven positive effects on cardiovascular endpoints. Because it is an inhibitor of the hepatic transporters OATP1B1 and OATP1B3, two uptake transporters regulating the intrahepatic availability of statins, it increases the systemic exposure [...] Read more.
Background/Objectives: Bempedoic acid (BA) is a novel cholesterol-lowering agent with proven positive effects on cardiovascular endpoints. Because it is an inhibitor of the hepatic transporters OATP1B1 and OATP1B3, two uptake transporters regulating the intrahepatic availability of statins, it increases the systemic exposure of co-administered statins. This interaction could raise the risk of myopathy. We hypothesized that the drug interaction between BA and statins could be mitigated by staggered administration. Methods: This was a single-centre, open-label, randomized, two-arm, cross-over, phase I drug interaction trial in healthy volunteers (EudraCT-No: 2022-001096-13). The primary objective was to evaluate the OATP1B1 inhibitory effect of BA on exposure to pravastatin after simultaneous administration versus different schedules of staggered administration. A secondary objective was to evaluate the impact of SLCO1B1 genotypes (*1, *5, *15, *37) on pravastatin exposure. Pravastatin was administered in single oral doses of 40 mg at six visits. After a baseline visit with pravastatin alone, BA was dosed to steady state at the approved oral dose of 180 mg. Outcome measures were the area under the plasma concentration–time curve, extrapolated to infinity (AUC∞) and Cmax of pravastatin, 3α-hydroxy-pravastatin (pravastatin 3-iso), and pravastatin lactone, and their geometric mean ratios (GMRs) of different schedules of administration. Log-transformed AUC∞ and Cmax were compared with one-way ANOVA with a 90% confidence interval (CI). Results: Fourteen participants completed all visits. At BA steady state, the GMRs of pravastatin AUC∞ and Cmax were 1.80 (90% CI 1.31–2.46) and 1.95 (90% CI 1.40–2.72), respectively, compared to baseline. There was no significant difference in pravastatin exposure between simultaneous vs. staggered administration. There was no statistically significant difference in pravastatin 3-iso or pravastatin lactone between different administration modes. For the AUC∞ of pravastatin and pravastatin 3-iso, haplotype was a significant source of variation (63% and 20%, respectively), while the type of administration (simultaneous vs. staggered) had no significant impact. Conclusions: The increase in pravastatin exposure with concomitant intake of BA was larger than expected. There was no significant difference between simultaneous vs. staggered administration of pravastatin and BA, possibly due to a population that was heterogenous in SLCO1B1 haplotypes. Full article
(This article belongs to the Special Issue Pharmacokinetic and Pharmacodynamic Considerations for Drugs Used in the Treatment of Cardiovascular Diseases)
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17 pages, 1696 KiB  
Article
Oral Drug Absorption and Drug Disposition in Critically Ill Cardiac Patients
by Lars-Olav Harnisch, Jürgen Brockmöller, Anne Hapke, Juliane Sindern, Ellen Bruns, Ruben Evertz, Karl Toischer, Bernhard C. Danner, Dorothee Mielke, Veit Rohde and Tammam Abboud
Pharmaceutics 2023, 15(11), 2598; https://doi.org/10.3390/pharmaceutics15112598 - 7 Nov 2023
Cited by 1 | Viewed by 1918
Abstract
(1) Background: In critically ill cardiac patients, parenteral and enteral food and drug administration routes may be used. However, it is not well known how drug absorption and metabolism are altered in this group of adult patients. Here, we analyze drug absorption and [...] Read more.
(1) Background: In critically ill cardiac patients, parenteral and enteral food and drug administration routes may be used. However, it is not well known how drug absorption and metabolism are altered in this group of adult patients. Here, we analyze drug absorption and metabolism in patients after cardiogenic shock using the pharmacokinetics of therapeutically indicated esomeprazole. (2) Methods: The pharmacokinetics of esomeprazole were analyzed in a consecutive series of patients with cardiogenic shock and controls before and after elective cardiac surgery. Esomeprazole was administered orally or with a nasogastric tube and once as an intravenous infusion. (3) Results: The maximum plasma concentration and AUC of esomeprazole were, on average, only half in critically ill patients compared with controls (p < 0.005) and remained lower even seven days later. Interestingly, esomeprazole absorption was also markedly compromised on day 1 after elective surgery. The metabolites of esomeprazole showed a high variability between patients. The esomeprazole sulfone/esomeprazole ratio reflecting CYP3A4 activity was significantly lower in critically ill patients even up to day 7, and this ratio was negatively correlated with CRP values (p = 0.002). The 5′-OH-esomeprazole and 5-O-desmethyl-esomeprazol ratios reflecting CYP2C19 activity did not differ significantly between critically ill and control patients. (4) Conclusions: Gastrointestinal drug absorption can be significantly reduced in critically ill cardiac patients compared with elective patients with stable cardiovascular disease. The decrease in bioavailability indicates that, under these conditions, any vital medication should be administered intravenously to maintain high levels of medications. After shock, hepatic metabolism via the CYP3A4 enzyme may be reduced. Full article
(This article belongs to the Special Issue Pharmacokinetic and Pharmacodynamic Considerations for Drugs Used in the Treatment of Cardiovascular Diseases)
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