Population pharmacokinetics of lumefantrine in the presence of nevirapine in HIV infected children Phytomédecine: Une source abondante de thérapeutiques sûres et efficaces pour relancer la production pharmaceutique locale
Main Article Content
Abstract
Background: The geographical overlap of malaria and HIV in sub-Saharan Africa poses a major public health challenge, which is further worsened by the potential interactions between antimalarial and antiretroviral drugs when co-administered.
Objective: This study aimed to determine the population pharmacokinetic parameters of lumefantrine in the presence of nevirapine in HIV infected children. Methods: A sparse pharmacokinetic study of lumefantrine was conducted in children living with HIV and being treated with nevirapine-based antiretroviral drug combination and were also being treated for malaria using artemether/lumefantrine (AL) combination. Blood sampling was performed at baseline (pre-dose, day 0) and at three additional time points selected from days 1, 3, 7, 14, 21, or 28. The pharmacokinetic modeling of lumefantrine was performed using a population approach with a non-linear mixed effect model (NLMEM) using a software program MonolixSuite® 2019 version R2, Lixoft, Antony, France, (http://www.lixoft.com).
Results: Lumefantrine pharmacokinetics were best described by a three-compartment disposition model with transit-compartment absorption and additive residual error. The mean transit time was 1.16 h, and apparent elimination clearance was estimated at 0.84, with low between-subject variability. Concomitant nevirapine use was associated with a modest, non-significant 6% increase in apparent lumefantrine clearance (P > 0.05). Allometric weight-based models did not significantly improve model performance. Diagnostic plots and visual predictive checks confirmed adequate model fit and predictive performance.
Conclusion: Nevirapine-based antiretroviral therapy did not result in clinically meaningful alteration of lumefantrine pharmacokinetics in children. These findings support continued use of standard weight-based artemether-lumefantrine dosing in HIV-infected paediatric populations receiving nevirapine.
Résumé
Contexte: De nombreux systèmes de santé dépendent largement des phytomédicaments. Cependant, ces agents thérapeutiques font l'objet de critiques en raison du manque d'informations sur leur qualité, leur innocuité et leur efficacité.
Objectifs: Cette étude vise à rassembler les données scientifiques sur la disponibilité, l'innocuité et l'efficacité des phytomédicaments, à mettre en évidence les méthodes disponibles pour optimiser leur qualité et à souligner la nécessité de relancer leur production locale.
Méthodes: Environ 1 000 articles évalués par des pairs provenant de 5 bases de données (Google Scholar, Pubmed, Scopus, Web of Science et Science Direct) ont été examinés afin d'extraire les informations pertinentes sur ce sujet de discussion.
Résultats: On recense plus de 50 000 espèces végétales rien qu'en Afrique subsaharienne, dont plus de 5 000 sont déjà utilisées à des fins médicinales. Cependant, seules quelques-unes ont fait l'objet d'études approfondies. Les pays et institutions africains, notamment les chercheurs, ont continué à répertorier les plantes médicinales importantes à mesure que les connaissances s'enrichissent et que de nouvelles informations émergent. Les phytomédicaments sont reconnus pour leur utilité dans la prise en charge de nombreuses maladies, mais des difficultés subsistent en matière de standardisation, de formulation et d'utilisation sans risque dans certains cas. Il existe désormais plusieurs moyens de relever ces défis.
Conclusion: Il est clair que notre système de santé repose en grande partie sur les médecines traditionnelles et que le monde se tourne à nouveau vers la nature. L'Afrique regorge de plantes médicinales dont les composants actifs peuvent être transformés en formes galéniques appropriées; ce qui souligne la nécessité de relancer la production locale de phytomédicaments.
Downloads
Article Details
Issue
Section
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
Share
References
1. Muhammad BY, Awaisu A (2008). The need for enhancement of research, development and commercialization of natural medicinal products in Nigeria: Lessons from the Malaysian experience. African Journal of Traditional, Complementary and Alternative Medicine 5(2): 120-130.
2. Schulz V, Hansel R, Blumenthal M, Tyler VE (Eds.) (2004). Rational Phytotherapy: A Reference Guide for Physicians and Pharmacists, 5th edition. Springer - Verlag, Berlin Heidelberg.
3. Pandey A, Tripathi, S, (2014). Concept of standardized extraction and pre phytochemical screening strategies for herbal drugs. Journal of
Pharmacognosy and Phytochemistry 2(5): 115-119.
4. Azwanida NN (2015). A review on the extraction methods use in medicinal plants, principle, strength and limitation. Journal of Medicinal and Aromatic Plants 4(3). http://dx.doi.org/10.4172/2167-0412.100016.
5. World Health Organization (WHO) Technical Report (2018). Series no. 1010. WHO Guidelines on Good Herbal Processing Practices for Herbal Medicines.
6. Kumar S, Baldi A, Sharma DK (2020). Phytosomes: A Modernistic approach for novel herbal drug delivery- Enhancing bioavailability and revealing endless Frontier of Phytopharmaceuticals. Journal of Developing Drugs 9(2). DOI: 10.35248/2329-6631.20.9.195.
7. Ansari SH, Islam F, Sameem M (2012). Influence of nanotechnology on herbal drugs: A review. Journal of Advanced Pharmaceutical Technology and Research 3(3): 142-146.
8. De Moraes MO, Frota FA, Bezzerra FA, Costa-Lotufo LV, Pessoa C, De Moraes ME (2006). Safety and efficacy of phytomedicines. Advanced Phytotherapy 2: 213-224.
9. Calixto JB (2000). Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents). Brazilian Journal of Medical and Biological Research 33(2): 179-189.
10. Mohamed I, Shuid A, Borhanuddin B, Fozi N (2012). The Application of phytomedicine in modern drug development. The Internet Journal of Herbal and Plant Medicine 1(2).
11. Karunamoorthi K, Jegajeevanram K, Vijayalakshmi J, Mengistie E (2013). Traditional medicinal plants: A source of phytotherapeutic modality in resourceconstrained health care settings. Journal of Evidence-Based Complementary and Alternative Medicine 18(1):67-74.
12. Krishnaprabu DS (2020). Therapeutic potential of medicinal plants: A review. Journal of Pharmacognosy and Phytochemistry 9(2):2228-
2233.
13. Mahomoodally MF (2013). Evidence-based complementary and alternative medicine traditional medicines in Africa: An appraisal of ten
potent African medicinal plants. Evidence-Based Complementary and Alternative Medicine 2013:1-14.
14. Adetunbi RO (2020). African traditions and the modern healthcare delivery system in the contemporary Nigerian Society. African Journal of
Culture, History, Religion and Traditions 2(1):1-9.
15. Okigbo RN, Mmeka EC (2006). An appraisal of phytomedicine in Africa. KMITL Science and Technology Journal 6(2):83-94.
16. Schultes RE (1984). Medicinal plants and traditional medicine in Africa. Journal of Ethnopharmacology 10(3):332-333.
17. Hamby EB (2004). The roots of healing: Archaeological and historical investigations of African-American Herbal Medicine. PhD
dissertation. University of Tennessee. Available from: https://trace.tennessee.edu/utk_graddiss/4543/
18. Iwu MM. Handbook of African Medicinal Plants, Second Edition. CRC Press. ISBN-13 978-1466571976.
19. African Herbal Pharmacopoeia, 2026. Edited By David R. Katerere, Thomas Brendler, Ulrich Feiter, Mohamad Fawzi Mahomoodally, Lawrance Denzil Phillips. CRC Press. ISBN 9780815374244.
20. The South African Herbal Pharmacopoeia, 2022. Academic Press. ISBN: 978-0-323-99794-2.
21. West African Herbal Pharmacopoeia, 2013. WAHO West African Health Organization (WHO) BoboDioulasso (Burkina Faso). KS Printcraft GH. LTD, Kumasi, Ghana.
22. Ghana Herbal Pharmacopoeia, 2015. Science and Technology Policy Research Institute, Council for Scientific and Industrial Research. ISBN-13 978998809731X.
23. Nigerian Herbal Pharmacopoeia - Abuja FMH, 2008. ISBN: 9789780880200. World Health Organization(WHO).
24. Emeje M, Bekoe EO, Graz B, Willcox M (2023). Traditional Medicine Development in Africa: Opinion. Journal of Integrative and Complementary Medicine 29(6-7). DOI. https://orcid.org/0000-0002-0202-5426.
25. Herbarium - Nigeria Natural Medicine Development Agency. Available at: https://nnmda.gov.ng. Accessed on March 21, 2026.
26. Ogunwande IA, Walker TM, Setzer WN (2019). A review of aromatic herbal plants of medicinal importance from Nigeria. Natural Products
Communication 2(12): 1311-1316.
27. Lokesh Prasad MS, Kalaskar PG, Chandrasekar SB, Umashankar C, Pawar AT (2017). Formulation and evaluation of herbal formulations (Ointment, Cream, Gel) containing Tridax procumbens and Areca catechu. Journal of Scientific and Innovative Research 6(3): 97-100.
28. Baldi A, Singh PA (2017). Evidence based pharmacology of herbal formulations: need of the hour. Journal of Complementary Medicine and
Alternative Healthcare 3(3): 2572-1232.
29. Iyer M, Gujjari AK, Rao RN, Gowda DV, Srivastava A (2016). Biomedical applications of phytomedicines: Dental perspective. Dent Hypotheses 7: 34-41.
30. World Health Organization (1993). Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicines. Retrieved from
http://apps.who.int/medicinedocs/en/d/Jh2946e/5.3.html on 11th August 2020.
31. World Health Organization (2007). WHO guidelines for assessing quality of herbal medicines with reference to contaminants and residues. Retrieved from http://apps.who.int/medicinedocs/documents/s14878e/s14878e.pdf on 11th August 2020.
32. Bent S (2008). Herbal medicine in the United States: Review of efficacy, safety, and regulation. Journal of General Internal Medicine 23(6): 854-859.
33. Mosihuzzaman M, Choudhary MI (2008). Protocols on safety, efficacy, standardization, and documentation of herbal medicine. Pure and Applied Chemstry 80(10): 2195-2230.
34. Lee C, Yu M, Lin C, Lee M, Wei J, Shih H (2015). Efficacy and safety of herbal medicine yun-cai tea in the treatment of hyperlipidemia: A double-blind placebo-controlled clinical trial. Chinese Journal of Integrative Medicine, 21(8): 587-593.
35. Moreira D, Teixeira SS, Monteiro MH, De-Oliveira AC, Paumgartten FJR (2014). Traditional use and safety of herbal medi c ines. Revista Brasileira de Farmacognosia 24: 248-257.
36. Ekor M (2013). The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Fronters in
Pharmacology 4:177. doi: 10.3389/fphar.2013.00177
37. Taylor JA, Weber W, Standish L, Quinn H, Goesling J, McGann M, Calabrese C (2003). Efficacy and safety of Echinacea in treating upper respiratory tract infections in children: A Randomized Controlled Trial. JAMA 290(21): 2824-2830.
38. Ankrah N, Nyarko AK, Addo PGA, Ofosuhene M, Dzokoto C, Marley E, Addae M, Ekuban FA (2003). Evaluation of efficacy and safety of a herbal medicine used for the treatment of malaria. Phytotherapy Research 17(6):697-701.
39. Tufail T, Ain HRU, Ijaz A, Nasir MA, Ikram A, Noreen S, Arshad MT, Abdulahi MA (2025). Neem (Azadirachta indica): A miracle herb: Panacea for all ailments. Food Science and Nutrition 13: e70820.
40. Fazio S, Pouso J, Dolinsky D, Fernandez A, Hernandez M, Clavier G, Hecker M (2009). Tolerance, safety and efficacy of Hedera helix extract in inflammatory bronchial diseases under clinical practice conditions: a prospective, open, multicentre postmarketing study in 9657 patients. Phytomedicine 16(1): 17-24.
41. Ghazi-Moghadam K, Inançl? H, Bazazy N, Plinkert PK, Efferth T, Sertel S (2012). Phytomedicine in Otorhinolaryngology and Pulmonology: Clinical Trials with Herbal Remedies. Pharmaceuticals 5: 853-874.
42. Agrawal N, Gupta ND, Garg AK, Sharma V, Singh R (2014). Resurgence of phytomedicine use in dentistry. American Journal of Phytomedicine and Clinical Therapeutics 2(3):322-333.
43. Velaskar S, Nayak CS, Torsekar RG, Viswanath V, Khopkar U, Saraf V, Kulkarni S, Shindikar A, Patil, A, Patil S, Parikh H, Suthar AC, Vijaysingh Chauhan V, Padigaru M, Chakrabarti D, Sharma S (2016). Efficacy and safety of two doses of Sphaeranthus indicus extract in the management of plaque Psoriasis: A randomized, double blind, placebocontrolled Phase II trial. American Journal of Dermatology and Venerology 5(1): 6-15.
44. Abdullah SS, Alkhoshaiban AS, Mani V, Akkawi ME, Ming LC (2016). Safety and efficacy of herbal tea for patients with diabetes mellitus. Arch Pharmacy Practice 7:5-10.
45. Naber KG (2013). Efficacy and safety of the phytotherapeutic drug Canephron® N in prevention and treatment of urogenital and gestational disease: review of clinical experience in Eastern Europe and Central Asia. Research and Reports in Urology 5:39-46.
46. Chandira M, Jayakar B (2010). Formulation and Evaluation of herbal tablets containing Ipomoea digitate Linn extract. International Journal of Pharmaceutical Science Review and Research 3(1):101-110.
47. Anbu JS, Roslizam BS, Anandarajagopal K, Anita, GK, Khan A, Muthumani M (2018). Formulation and evaluation of herbal capsules containing dried ethanol extract of Gnetum gnemon fruits. International Journal of Pharmacy and Pharmaceutical Research 12(1): 273-280.
48. Dos Santos ECF, Machado JCB, Ferreira MRA, Soares LAL (2025). Strategies to overcome challenges in formulating tablets from dried plant extracts: A comprehensive review. AAPS PharmSciTech 47(1): 14. Doi: 10.1208/s12249-025-03255-9.