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Bioavailability of paracetamol with/without caffeine in Egyptian patients with hepatitis C virus

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

This study investigates the involvement of liver dysfunction in the modulation of paracetamol pharmacokinetic profile in genotype-4 HCV patients treated with either paracetamol alone (Para) or in combination with caffeine (Para-Caf).

Methods

Twenty healthy volunteers and 20 Child-Pugh B HCV patients, each divided into two equal subgroups, were examined, whose liver/kidney functions were correlated with their main clinical manifestation. After an overnight fasting, healthy and hepatic subjects received either a single dose of Para (1000 mg paracetamol) or Para-Caf (1000 mg paracetamol/130 mg caffeine). Two milliliters of saliva samples were collected prior to and at different time-intervals after drug administration and analyzed using HPLC.

Results

There was a noticeable increase in the mean concentration time profile of salivary paracetamol concentrations in hepatic patients, with concomitant decrease in paracetamol clearance (CLT), along with induction in the primary pharmacokinetic (PK) parameters, C max, AUC(0–8 h) and AUC(0–∞) (by about 95, 82, and 64 %, respectively, after treatment with Para, and 98, 96, and 101 %, respectively, after treatment with Para-Caf), when compared with the corresponding parameters in healthy subjects. Additionally, the healthy subjects treated with Para-Caf exhibited bioinequivalent increase in C max, K a, and t 1/2 with decrease in T max when compared with the healthy individuals treated with Para alone. A similar pattern was recorded in hepatic patients after addition of caffeine to paracetamol, with even augmented significant increase in K a and t 1/2 (by 100 and 32 %, respectively).

Conclusions

Liver dysfunction modified the PK of paracetamol expressed as earlier effective paracetamol concentration, with obvious decrease in its clearance. Caffeine induced faster absorption (evidenced by shorter T max and higher K a) and prolonged t 1/2 of paracetamol, the effects that were more profound in hepatic patients. Further studies are needed to evaluate the influence of liver damage on paracetamol pharmacokinetics whenever repeated dosing is applied, to avoid possible drug accumulation.

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Acknowledgments

The authors would like to express their deepest appreciation and gratitude to Dr. Mohey Elmazar, Professor of Pharmacology and Toxicology, Dean of Faculty of Pharmacy, The British University, Cairo, Egypt, for his help in the management of the statistical analysis in the study. The authors also thank all participating patients and volunteers. This work was financially supported by the internal research project 83/A, a grant from Theodor Bilharz Research Institute (TBRI).

Authors’ contributions

NME contributed to the conception and design of the work, data analysis, and interpretation of results and writing of the manuscript. ASH performed the bioavailability study, data collection, and analysis. SHS was involved in the study protocol, data acquisition, analysis, and tabulation of results. AAA was involved in interpretation of results and writing of the manuscript. RA supervised the clinical study and was involved in interpretation of results. AHA was involved in conceptualizing the current study, design of the work, and revising of the manuscript. AMM was involved in the study protocol and data analysis. SSB contributed to the conception and design of the work, interpretation of results, and revising of the manuscript. All authors critically read and approved the final manuscript.

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Authors and Affiliations

  1. Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt

    Naglaa M. El-Lakkany, Ahmed S. Hendawy, Sayed H. Seif el-Din & Sanaa S. Botros

  2. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Nasr city, Cairo, Egypt

    Ahmed A. Ashour, Abdel-Aziz H. Abdel-Aziz & Ahmed M. Mansour

  3. Department of Hepatogastroenterology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba, P.O. Box 30, Giza, 12411, Egypt

    Raafat Atta

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  1. Naglaa M. El-Lakkany
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Corresponding author

Correspondence to Naglaa M. El-Lakkany.

Ethics declarations

The study was initiated after approval by the institutional review board (IRB) committee of TBRI and are in accordance with the ethical principles of Helsinki Declaration (1964) and its later amendments, ICH Guidelines for Good Clinical Practice (GCP) (December, 2014), and other applicable regulations.

Informed consent

Patients agreeing to participate in the study were admitted to the hepatogastroenterology department of TBRI. All the subjects were informed with objectives, treatments, potential risks, dates, and activities during the clinical part of the study. A written consent form was signed by each enrolled subject.

Conflict of interest

The authors declare that they have no competing interests.

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El-Lakkany, N.M., Hendawy, A.S., Seif el-Din, S.H. et al. Bioavailability of paracetamol with/without caffeine in Egyptian patients with hepatitis C virus. Eur J Clin Pharmacol 72, 573–582 (2016). https://doi.org/10.1007/s00228-016-2025-1

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  • DOI: https://doi.org/10.1007/s00228-016-2025-1

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