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Pre-clinical compartmental pharmacokinetic modeling of 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) as a photosensitizer in rat plasma by validated HPLC method

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Abstract

A second-generation chlorin-based photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) has shown tremendous therapeutic potential in clinical trials in the treatment of esophageal cancer. Herein, we have developed and validated a bioanalytical method for estimation of HPPH in rat plasma using High Performance Liquid Chromatography (HPLC) with a photo diode array (PDA) detector. The method was applied for carrying out pharmacokinetic study of HPPH. Further pharmacokinetic modeling was carried out to understand the compartment kinetics of HPPH. The developed method was fully validated as per the United States Food and Drug Administration (US-FDA) guidelines for bioanalytical method validation. The linearity of the method was in the range of 250–8000 ng mL−1, and the plasma recovery was found to be 70%. Pharmacokinetic parameters were evaluated and compared via non-compartment analysis and compartment modeling after the intravenous (i.v.) bolus administration in rats using Phoenix WinNonlin 8.0 (Certara™, USA). From the obtained results, we hypothesize that the HPPH complies with two compartmental pharmacokinetic model. Furthermore, it was observed that HPPH has the rapid distribution from the central compartment to peripheral compartment along with slow elimination from peripheral compartment.

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Authors and Affiliations

  1. Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS-PILANI), Pilani Campus, Rajasthan, India

    Kowthavarapu Venkata Krishna & Sunil Kumar Dubey

  2. Department of Biotechnology, Birla Institute of Technology and Science, Pilani (BITS-PILANI), Dubai Campus, Dubai, United Arab Emirates

    Ranendra Narayana Saha

  3. RNA Structure and Design Section, RNA Biology Laboratory (RBL), Center for Cancer Research, National Cancer Institute – Frederick, Frederick, MD, USA

    Anu Puri & Bruce A. Shapiro

  4. Basic Science Program, CIP, Frederick National Laboratory for Cancer Research sponsored by the National Cancer Institute, Frederick, MD, USA

    Mathias Viard

Authors
  1. Kowthavarapu Venkata Krishna
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  2. Ranendra Narayana Saha
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  3. Anu Puri
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  4. Mathias Viard
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  5. Bruce A. Shapiro
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  6. Sunil Kumar Dubey
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Correspondence to Sunil Kumar Dubey.

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Electronic supplementary information (ESI) available. See DOI: 10.1039/c8pp00339d

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Krishna, K.V., Saha, R.N., Puri, A. et al. Pre-clinical compartmental pharmacokinetic modeling of 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) as a photosensitizer in rat plasma by validated HPLC method. Photochem Photobiol Sci 18, 1056–1063 (2019). https://doi.org/10.1039/c8pp00339d

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  • DOI: https://doi.org/10.1039/c8pp00339d

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