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Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers

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Abstract

Objective

Midodrine is an α-agonist prodrug of desglymidodrine used for the management of hypotension, and can also be used for hepatorenal syndrome and cirrhotic patients with tense ascites. The objective of the present work was to study the clinical pharmacokinetic parameters of midodrine and its active metabolite desglymidodrine in cirrhotic patients with tense ascites, which may help in dose selection and improve treatment outcome.

Method

This was a prospective, open-label, single-dose, parallel-group study. At first, a pilot study was performed on one healthy volunteer by taking serial blood samples at scheduled time intervals to validate the method of analysis and sampling times. The full study was then conducted by selecting 12 cirrhotic patients with tense ascites in one group and taking nine blood samples. We also selected five healthy volunteers as the control group and took 11 blood samples.

Results

Statistically significant differences were observed between the healthy volunteer group and the patients group in the area under the concentration versus time curve (AUC0–t ) and maximum plasma concentration (C max) values of midodrine and desglymidodrine. Based on the results of the pharmacokinetic analysis, the patient group was further subdivided into those receiving the interacting drug ranitidine (five patients) and those not receiving the interacting drug (seven patients).

Conclusions

Pharmacokinetic parameters of midodrine can differ significantly in cirrhotic patients with tense ascites from those in healthy individuals. Drug monitoring, dose adjustments, and drug–drug interactions should all be considered during therapy in this vulnerable patient group.

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Authors and Affiliations

  1. Department of Pharmaceutics, Egyptian Russian University, Badr City, Egypt

    Ahmed Ali

  2. Department of Clinical Pharmacy, Cairo University, Cairo, Egypt

    Samar Farid

  3. Department of Internal Medicine, Cairo University, Cairo, Egypt

    Mona Amin & Nouman Al-Garem

  4. Department of Pharmaceutics, Cairo University, Cairo, Egypt

    Mohamed Kassem

  5. Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Medhat Al-Ghobashy

  6. Bioanalysis Research Group, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Medhat Al-Ghobashy

  7. Qualiobia, Shebeen-Elquanater, Kafr Taha, Egypt

    Ahmed Ali

Authors
  1. Ahmed Ali
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  2. Samar Farid
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  3. Mona Amin
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  4. Mohamed Kassem
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  5. Nouman Al-Garem
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  6. Medhat Al-Ghobashy
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Corresponding author

Correspondence to Ahmed Ali.

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Funding

This study was self-funded.

Conflicts of interest

Ahmed Ali, Samar Farid, Mona Amin, Mohamed Kassem, Nouman Al-Garem, and Medhat Al-Ghobashy have declared that there are no conflicts of interest.

Ethical approval

The Research Ethics Committee of the Faculty of Pharmacy, Cairo University, Cairo, Egypt (ethical registration number PI 951).

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Ali, A., Farid, S., Amin, M. et al. Comparative Clinical Pharmacokinetics of Midodrine and Its Active Metabolite Desglymidodrine in Cirrhotic Patients with Tense Ascites Versus Healthy Volunteers. Clin Drug Investig 36, 147–155 (2016). https://doi.org/10.1007/s40261-015-0359-6

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  • DOI: https://doi.org/10.1007/s40261-015-0359-6

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