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CC BY 4.0 · Journal of Health and Allied Sciences NU 2024; 14(S 01): S104-S109
DOI: 10.1055/s-0044-1786996
Original Article

Dynamic Interplay of Age and Protein Malnutrition on the Pharmacokinetic Profile of Acetaminophen in Wistar Rats

Varsha Augustin
1   Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Nitte University Centre for Animal Research and Experimentation (NUCARE), Deralakatte, Mangalore, Karnataka, India
,
Vinitha D'Souza
1   Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Nitte University Centre for Animal Research and Experimentation (NUCARE), Deralakatte, Mangalore, Karnataka, India
,
Madhura R. J.
1   Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Nitte University Centre for Animal Research and Experimentation (NUCARE), Deralakatte, Mangalore, Karnataka, India
,
Murali Badanthadka 
1   Nitte (Deemed to be University), NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Department of Nitte University Centre for Animal Research and Experimentation (NUCARE), Deralakatte, Mangalore, Karnataka, India
,
B.S. Mamatha 
2   Nitte (Deemed to be University), NUCSER, Paneer Campus, Deralakatte, Mangalore, Karnataka, India
,
K. Vijayanarayana
3   Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
› Author Affiliations Financial Disclosure This work was supported by Nitte (Deemed to be University) (N/RG/NUFR2/NGSMIPS/2022/02).
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Abstract

Objectives Age and protein malnutrition (PMN) are well-known determinants of drug pharmacokinetics. The combined influence of age and nutrition on the pharmacokinetics of acetaminophen (APAP) remains insufficiently explored; therefore, this study investigates the role of age and PMN on APAP pharmacokinetics.

Materials and Methods Wistar rat weanlings were divided into four groups. Groups ND-5 (n = 6) and ND-18 (n = 6) were fed with normal diet (ND, 18% protein) and groups LPD-5 (n = 6) and LPD-18 (n = 6) were fed with low-protein diet (LPD, 10%) for 5 and 18 months, respectively. Blood samples were collected at different time intervals (0, 0.5, 1, 3, 6, 24, 36, and 48 hours), and plasma was separated and analyzed for APAP using high-performance liquid chromatography. Pharmacokinetic data was analyzed by the noncompartmental model using Phoenix WinNonlin 8.3 software.

Results The pharmacokinetic parameters of APAP were elevated in both LPD groups compared with their age-matched controls. The average area under the curve was increased by approximately 131% (LPD-5) and 17.57% (LPD-18), and the average maximum plasma concentrations (Cmax) was increased by 33.5% (LPD-5) and 26.3% (LPD-18) compared with their respective age-matched controls. The average mean retention time was approximately 114% (LPD-5) and 17.4% (LPD-18) higher than their respective age-matched controls, whereas the clearance rate (Cl/F) and volume distribution (Vz/F) of the drug were significantly lower. Consequently, there was a 68.5% (ND-5) and 4.73% (ND-18) prolongation in the mean half-life of APAP.

Conclusion The altered pharmacokinetics may arise from the intricate interplay of dietary and age influences on physiology, protein binding, and cytochrome P450enzyme activity/expression. However, the exact reason requires further investigation for a better understanding of vulnerable populations.

Keywords

acetaminophen - age - noncompartmental model - protein malnutrition - pharmacokinetics - rats

Ethics Committee Approval

Ethics Committee Approval: All the animal experiments were conducted as per the guidelines of the CPCSEA (Committee for the Purpose of Control and Supervision of Experiments on Animals) with approval number: NGSMIPS/Dec-2020/2022.


Approval date: 29th December 2020


Institution name: NGSM Institute of Pharmaceutical Sciences


Authors' Contributions

M.B. and V.A. conceptualized and designed the study. V.A., V.D., M.R.J. were involved in data collection and writing of the manuscript. V.A., M.B.S., and V.K. contributed to analysis or interpretation. V.A. and V.D. helped in literature search.




Publication History

Article published online:
03 June 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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