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Population pharmacokinetic analysis of bisoprolol in type 2 diabetic patients with hypertension

  • Pharmacokinetics and Disposition
  • Published:
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Abstract

Purpose

Given that it has been reported that type 2 diabetes mellitus may affect the pharmacokinetics of a large number of drugs and that there are still no published population pharmacokinetic (PopPK) analyses in routinely treated patients with hypertension and type 2 diabetes mellitus as comorbid condition, the aim of this study was to determine PK variability of bisoprolol in 70 Serbian patients using the PopPK approach.

Methods

PopPK analysis was conducted using a nonlinear mixed effects model (NONMEM), version 7.3.0 (Icon Development Solutions). In our patients, a total daily dose of bisoprolol ranged from 1.25 to 10 mg. The drug was administrated orally as a single daily dose or in two divided doses per day.

Results

A wide range of the drug concentrations were noted (1–103 ng/mL) in the population consisted of the adult patients with type 2 diabetes mellitus. From a total of 21 separately assessed covariates, our results indicated that only creatinine clearance could have a potential impact on the variability of the clearance of bisoprolol.

Conclusion

Routine assessment of renal function should be carried out before the initiation of treatment with bisoprolol in order to individualize the dose and to prevent possible accumulation and adverse drug reactions.

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Acknowledgments

The authors would like to thank Slavoljub Živanović from the Laboratory for Functional Genomics and Proteomics, Research Center for Biomedicine, Faculty of Medicine, University of Niš, Serbia, for determination of the plasma concentrations of bisoprolol using the standard high-performance liquid chromatography system with fluorometric detector.

Authors’ individual contributions

S.M., V.N.N., S.M.J, and J.R.M. were involved in conception and design of the study. S.M., A.J., D.R., V.N.N., S.M.J, M.P., and J.R.M. were involved in acquisition, analysis, and interpretation of the data. S.M., A.J., and J.R.M. drafted the manuscript and all other authors critically revised the manuscript. All authors gave final approval of the manuscript to be published.

Funding

The study was supported by the Serbian Ministry of Education and Science grant no. III41007 and grant no. 175007.

Author information

Authors and Affiliations

  1. Faculty of Medicine, University of Niš, Blvd Zorana Djindjića 81, Niš, 18000, Serbia

    Stefan Momčilović & Andriana Jovanović

  2. Department of Endocrinology, Faculty of Medicine, University of Niš, Niš, Serbia

    Danijela Radojković & Milica Pešić

  3. Clinic for Endocrinology, Clinical Center of Niš, Niš, Serbia

    Danijela Radojković & Milica Pešić

  4. Department of Pharmacology and Toxicology, Faculty of Medicine, University of Niš, Niš, Serbia

    Valentina N. Nikolić

  5. Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

    Slobodan M. Janković & Jasmina R. Milovanović

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  1. Stefan Momčilović
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  4. Valentina N. Nikolić
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  7. Jasmina R. Milovanović
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Corresponding author

Correspondence to Stefan Momčilović.

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The research was conducted according to the ethical guidelines of the 1975 Helsinki Declaration and approved by the Ethics Committee of the Faculty of Medicine, University of Niš, Niš, Serbia (decision number: 01-9337-4).

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The authors declare that they have no conflicts of interest.

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Momčilović, S., Jovanović, A., Radojković, D. et al. Population pharmacokinetic analysis of bisoprolol in type 2 diabetic patients with hypertension. Eur J Clin Pharmacol 76, 1539–1546 (2020). https://doi.org/10.1007/s00228-020-02937-6

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  • DOI: https://doi.org/10.1007/s00228-020-02937-6

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