Effect of Chronopharmacology and Food on
            <i>in Vivo</i>
            Pharmacokinetic Profile of Mavacamten

Gajula, Siva Nageswara Rao; Talari, Sasikala; Nathani, Tanaaz Navin; Munjal, Vijay; Rahman, Zia Ur; Dandekar, Manoj P.; Sonti, Rajesh

doi:10.4155/bio-2023-0030

Bioanalysis

2023

DOI: 10.4155/bio-2023-0030

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Effect of Chronopharmacology and Food on in Vivo Pharmacokinetic Profile of Mavacamten

Siva Nageswara Rao Gajula

Sasikala Talari

Tanaaz Navin Nathani

et al.

Abstract: Aim: This study investigated the impact of food intake and circadian rhythms on the pharmacokinetics of mavacamten. Materials & methods: A sensitive bioanalytical method for quantifying mavacamten in rat plasma was developed and validated. This method was applied to assess the effect of chronopharmacology and food intake on the pharmacokinetics of mavacamten in rats. Results: A circadian variation at two doses resulted in significant changes in the volume of distribution, clearance and time of maximum plas… Show more

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Cited by 2 publications

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A Liquid Chromatography Coupled to Tandem Mass Spectrometry Method for Simultaneous Estimation of Saxagliptin and Avanafil: Application to Pharmacokinetic Drug‐Drug Interaction in Type 2 Diabetic Rat Model

Gajula,

Patil,

Rahman

et al. 2024

Separation Science Plus

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Erectile dysfunction is a common complication of type 2 diabetes. The combination of saxagliptin and avanafil can effectively manage both conditions in individuals with type 2 diabetes. However, evaluating the potential pharmacokinetic interactions for co‐administration of saxagliptin and avanafil is crucial. Here, we developed a sensitive bioanalytical method for simultaneously quantifying saxagliptin and avanafil in rat plasma using liquid chromatography hyphenated to triple quadrupole mass spectrometry. The chromatographic separation of saxagliptin, avanafil, and irbesartan (internal standard) was achieved on an Aquity BEH C18 column (100 × 2.1 mm, 1.7 µm), using 0.1% formic acid in water and acetonitrile as mobile phase with the gradient elution at a flow rate of 0.2 mL/min. Mass detection was carried out using selective reaction monitoring mode, with the product ions for saxagliptin, avanafil, and irbesartan being 180.2, 375.1, and 207.1 m/z, respectively. The developed liquid chromatography coupled to tandem mass spectrometry method was validated as per the US Food and Drug Administration guidelines in rat plasma. The validation findings confirmed the method's robustness and suitability for accurate quantification of saxagliptin and avanafil in rat plasma with the limit of quantification of 1 ng/mL for both the drugs and were linear in the range of 1–2000 ng/mL. The study found no significant pharmacokinetic interaction between saxagliptin and avanafil, suggesting they can be safely co‐administered to patients with type 2 diabetes.

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A Liquid Chromatography Coupled to Tandem Mass Spectrometry Method for Simultaneous Estimation of Saxagliptin and Avanafil: Application to Pharmacokinetic Drug‐Drug Interaction in Type 2 Diabetic Rat Model

Gajula,

Patil,

Rahman

et al. 2024

Separation Science Plus

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In Silico Tools to Thaw the Complexity of the Data: Revolutionizing Drug Research in Drug Metabolism, Pharmacokinetics and Toxicity Prediction

Sree Kommalapati,

Pilli,

Golla

et al. 2023

CDM

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In silico tool is the flourishing pathway for Researchers and budding chemists to strain the analytical data in a snapshot. Traditionally, drug research has heavily relied on labor-intensive experiments, often limited by time, cost, and ethical constraints. In silico tools have paved the way for more efficient and cost-effective drug development processes. By employing advanced computational algorithms, these tools can screen large libraries of compounds, identifying potential toxicities and prioritizing safer drug candidates for further investigation. Integrating in silico tools into the drug research pipeline has significantly accelerated the drug discovery process, facilitating early-stage decision-making and reducing the reliance on resource-intensive experimentation. Moreover, these tools can potentially minimize the need for animal testing, promoting the principles of the 3Rs (reduction, refinement, and replacement) in animal research. This paper highlights the immense potential of in silico tools in revolutionizing drug research. By leveraging computational models to predict drug metabolism, pharmacokinetics, and toxicity. Researchers can make informed decisions and prioritize the most promising drug candidates for further investigation. The synchronicity of In silico tools in this article on trending topics is insightful and will play an increasingly integral role in expediting drug development.

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Effect of Chronopharmacology and Food on in Vivo Pharmacokinetic Profile of Mavacamten

Cited by 2 publications

References 27 publications

A Liquid Chromatography Coupled to Tandem Mass Spectrometry Method for Simultaneous Estimation of Saxagliptin and Avanafil: Application to Pharmacokinetic Drug‐Drug Interaction in Type 2 Diabetic Rat Model

A Liquid Chromatography Coupled to Tandem Mass Spectrometry Method for Simultaneous Estimation of Saxagliptin and Avanafil: Application to Pharmacokinetic Drug‐Drug Interaction in Type 2 Diabetic Rat Model

In Silico Tools to Thaw the Complexity of the Data: Revolutionizing Drug Research in Drug Metabolism, Pharmacokinetics and Toxicity Prediction

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