Phcog.Net logo
Submit

BROWSE ALL JOURNALS

    SEE ALL 6 JOURNALS
    Journal of Pharmacology and PharmacotherapeuticsNOW IN
    Article

    Development of Physiologically Based Pharmacokinetic Model and Assessment of the Impact of Renal Underdevelopment in Preterm Infants on the Pharmacokinetics of Aminophylline

    Hari Prabhath Tummala1, Rachana Balusu1, Sahithi Thotakura1, Achyuth Kumar Pasnoor1, Arun Prasath Raju1, Shivakumar Mahadeva Lal2, Leslie Edwards Lewis3, Surulivelrajan Mallayasamy1★★ Corresponding author

    1. 1Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
    2. 2Center for Pharmacometrics and Molecular Discovery, Union University, Jackson, Tennessee, USA.
    3. 3Department of Paediatrics, Kasturba Medical College and Hospital, Manipal Academy of Higher Education, Manipal, Karnataka, India.

    CORRESPONDENCE

    Surulivelrajan Mallayasamy

    Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.

    msv.rajan@manipal.edu

    Received: 14-08-2021; Revised: 26-11-2021; Accepted: 28-01-2022.

    Volume 13, Issue 1 · pp. 72–78 · PUBLISHED 2022 · DOI: 10.1177/0976500X221080209

    View on J Pharmacol. Pharmacother. original site ↗

    ABSTRACT

    Objective: To develop a physiologically based pharmacokinetic (PBPK) model for individualization of the dosing regimen considering the physiological requirements of these preterm neonates. Methods: The study comprised preterm newborns with fewer than 34 weeks of gestation and six apneic episodes in 24 h. A PBPK model was created using PK-SIM (version 9, update 1, GitHub, San Francisco, CA, USA). A PBPK model is built using a typical loading dosage of 5 mg/kg and a maintenance dose of 1.5 mg/kg. Based on the verified base model, a PBPK model representing renal underdevelopment based on nRIFLE/pRIFLE categorization was developed. Results: The PK parameters of Aminophylline were computed using the PBPK model. As per the model prediction, T1/2 and area under the curve reduced as postnatal age increased, and in the event of renal underdevelopment, even while Cmax for patients under R (RISK), I (injury) was within the therapeutic range; it was greater compared to preterm without any renal complications. Mean Cmax (mol/L) was 59.53 and for R, I, and F (FAILURE) categories the values were 83.04, 99.69, and 126.98, respectively. Conclusion: The model was created using appropriate drug, study subject, and dosage protocol inputs. The established PBPK model could help in individualizing aminophylline dose in preterm babies.

    KEYWORDS

    Open in new tab

    REFERENCES

    As published

    Showing references and in-text citations exactly as published.

      Cite this article

      SELECT FORMAT

      Tummala, H. P., Balusu, R., Thotakura, S., Pasnoor, A. K., Raju, A. P., Lal, S. M., Lewis, L. E., & Mallayasamy, S. (2022). Development of Physiologically Based Pharmacokinetic Model and Assessment of the Impact of Renal Underdevelopment in Preterm Infants on the Pharmacokinetics of Aminophylline. Journal of Pharmacology and Pharmacotherapeutics, 13(1), 72–78. https://doi.org/10.1177/0976500X221080209