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Published in: AIDS Research and Therapy 1/2017

Open Access 01-12-2017 | Research

Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study

Authors: Tsitsi G. Monera-Penduka, Charles C. Maponga, Alan R. Wolfe, Lubbe Wiesner, Gene D. Morse, Charles F. B. Nhachi

Published in: AIDS Research and Therapy | Issue 1/2017

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Abstract

Background

Moringa oleifera Lam., an herb commonly consumed by HIV-infected people on antiretroviral therapy, inhibits cytochrome P450 3A4, 1A2 and 2D6 activity in vitro; and may alter the pharmacokinetics (PK) of antiretroviral drugs metabolized via the same pathways. However, in vitro drug interaction activity may not translate to a clinically significant effect. Therefore, the effect of moringa leaf powder on the PK of nevirapine in HIV-infected people was investigated.

Methods

Adult patients at steady-state dosing with nevirapine were admitted for 12-h intensive PK sampling following a 21-day herbal medicine washout. Blood sampling was repeated after 14 days of nevirapine and moringa (1.85 g leaf powder/day) co-administration. Nevirapine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. To assess the effect of moringa on nevirapine PK, the change in nevirapine area under the plasma concentration–time curve (AUC) was determined. The mean difference in pre- and post-moringa nevirapine, maximum concentration (Cmax) and concentration at 12 h (C12h) were also calculated. The PK parameters were compared by assessing the post/pre geometric mean ratios (GMRs) and associated 90% confidence intervals (CIs).

Results

Pharmacokinetics analyses were performed on the results from 11 participants for whom complete data were obtained. The post/pre GMRs and associated 90% CIs for nevirapine were 1.07 (1.00–1.14) for the AUC; 1.06 (0.98–1.16) for Cmax and 1.03 (0.92–1.16) for C12h.

Conclusion

Co-administration of Moringa oleifera Lam. leaf powder at the traditional dose did not significantly alter the steady-state PK of nevirapine.
Trial registration number NCT01410058 (ClinicalTrials.gov)
Literature
1.
go back to reference Meng Q, Liu K. Pharmacokinetic interactions between herbal medicines and prescribed drugs: focus on drug metabolic enzymes and transporters. Curr Drug Metab. 2014;15:791–807.CrossRefPubMed Meng Q, Liu K. Pharmacokinetic interactions between herbal medicines and prescribed drugs: focus on drug metabolic enzymes and transporters. Curr Drug Metab. 2014;15:791–807.CrossRefPubMed
2.
go back to reference Cho HJ, Yoon IS. Pharmacokinetic interactions of herbs with cytochrome p450 and p-glycoprotein. Evid Based Complement Altern Med. 2015. doi:10.1155/2015/736431. Cho HJ, Yoon IS. Pharmacokinetic interactions of herbs with cytochrome p450 and p-glycoprotein. Evid Based Complement Altern Med. 2015. doi:10.​1155/​2015/​736431.
3.
go back to reference Müller AC, Kanfer I. Potential pharmacokinetic interactions between antiretrovirals and medicinal plants used as complementary and African traditional medicines. Biopharm Drug Dispos. 2011;32:458–70.CrossRefPubMed Müller AC, Kanfer I. Potential pharmacokinetic interactions between antiretrovirals and medicinal plants used as complementary and African traditional medicines. Biopharm Drug Dispos. 2011;32:458–70.CrossRefPubMed
4.
go back to reference van den Bout-van den Beukel CJ, Koopmans PP, van der Ven AJ, De Smet PA, Burger DM. Possible drug-metabolism interactions of medicinal herbs with antiretroviral agents. Drug Metab Rev. 2006;38:477–514.CrossRefPubMed van den Bout-van den Beukel CJ, Koopmans PP, van der Ven AJ, De Smet PA, Burger DM. Possible drug-metabolism interactions of medicinal herbs with antiretroviral agents. Drug Metab Rev. 2006;38:477–514.CrossRefPubMed
5.
go back to reference Monera TG, Wolfe AR, Maponga CC, Benet LZ, Guglielmo J. Moringa oleifera leaf extracts inhibit 6 beta-hydroxylation of testosterone by CYP3A4. J Infect in Dev Ctries. 2008;2:379–83.CrossRef Monera TG, Wolfe AR, Maponga CC, Benet LZ, Guglielmo J. Moringa oleifera leaf extracts inhibit 6 beta-hydroxylation of testosterone by CYP3A4. J Infect in Dev Ctries. 2008;2:379–83.CrossRef
6.
go back to reference Monera TG, Maponga CC. Prevalence and patterns of Moringa oleifera use among HIV positive patients in Zimbabwe: a cross-sectional survey. J Public Health Afr. 2012;3:22–4.CrossRef Monera TG, Maponga CC. Prevalence and patterns of Moringa oleifera use among HIV positive patients in Zimbabwe: a cross-sectional survey. J Public Health Afr. 2012;3:22–4.CrossRef
7.
go back to reference Popoola JO, Obembe OO. Local knowledge, use pattern and geographical distribution of Moringa oleifera Lam. (Moringaceae) in Nigeria. J Ethnopharmacol. 2013;150:682–91.CrossRefPubMed Popoola JO, Obembe OO. Local knowledge, use pattern and geographical distribution of Moringa oleifera Lam. (Moringaceae) in Nigeria. J Ethnopharmacol. 2013;150:682–91.CrossRefPubMed
8.
go back to reference Taesotikul T, Navinpipatana V, Tassaneeyakul W. Selective inhibition of human cytochrome P450 1A2 by Moringa oleifera. Thai J Pharmacol. 2010;32:256–8. Taesotikul T, Navinpipatana V, Tassaneeyakul W. Selective inhibition of human cytochrome P450 1A2 by Moringa oleifera. Thai J Pharmacol. 2010;32:256–8.
9.
go back to reference Awortwe C, Bouic PJ, Masimirembwa CM, Rosenkranz B. Inhibition of major drug metabolizing CYPs by common herbal medicines used by HIV/AIDS patients in Africa—implications for herb-drug interactions. Drug Metab Lett. 2014;7:83–95.CrossRefPubMedPubMedCentral Awortwe C, Bouic PJ, Masimirembwa CM, Rosenkranz B. Inhibition of major drug metabolizing CYPs by common herbal medicines used by HIV/AIDS patients in Africa—implications for herb-drug interactions. Drug Metab Lett. 2014;7:83–95.CrossRefPubMedPubMedCentral
10.
go back to reference Riska P, Lamson M, MacGregor T, Sabo J, Hattox S, Pav J, Keirns J. Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab Dispos. 1999;27:895–901.PubMed Riska P, Lamson M, MacGregor T, Sabo J, Hattox S, Pav J, Keirns J. Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab Dispos. 1999;27:895–901.PubMed
11.
go back to reference Wen B, Chen Y, Fitch WL. Metabolic activation of nevirapine in human liver microsomes: dehydrogenation and inactivation of cytochrome P450 3A4. Drug Metab Dispos. 2009;37:1557–62.CrossRefPubMed Wen B, Chen Y, Fitch WL. Metabolic activation of nevirapine in human liver microsomes: dehydrogenation and inactivation of cytochrome P450 3A4. Drug Metab Dispos. 2009;37:1557–62.CrossRefPubMed
12.
go back to reference Manosuthi W, Athichathanabadi C, Uttayamakul S, Phoorisri T, Sungkanuparph S. Plasma nevirapine levels, adverse events and efficacy of antiretroviral therapy among HIV-infected patients concurrently receiving nevirapine-based antiretroviral therapy and fluconazole. BMC Infect Dis. 2007;7:1–8.CrossRef Manosuthi W, Athichathanabadi C, Uttayamakul S, Phoorisri T, Sungkanuparph S. Plasma nevirapine levels, adverse events and efficacy of antiretroviral therapy among HIV-infected patients concurrently receiving nevirapine-based antiretroviral therapy and fluconazole. BMC Infect Dis. 2007;7:1–8.CrossRef
13.
go back to reference de Maat MMR, Hoetelmans RMW, Mathôt RAA, van Gorp ECM, Meenhorst PL, Mulder JW, Beijnen JH. Drug interaction between St John’s wort and nevirapine. AIDS. 2001;15:420–1.CrossRefPubMed de Maat MMR, Hoetelmans RMW, Mathôt RAA, van Gorp ECM, Meenhorst PL, Mulder JW, Beijnen JH. Drug interaction between St John’s wort and nevirapine. AIDS. 2001;15:420–1.CrossRefPubMed
15.
go back to reference Monera-Penduka TG, Jani ZT, Maponga CC, Mudzengi J, Morse GD, Nhachi CFB. Quality and labeling information of Moringa oleifera products marketed for HIV-infected people in Zimbabwe. J Public Health Afr. 2016;7:84–8. Monera-Penduka TG, Jani ZT, Maponga CC, Mudzengi J, Morse GD, Nhachi CFB. Quality and labeling information of Moringa oleifera products marketed for HIV-infected people in Zimbabwe. J Public Health Afr. 2016;7:84–8.
17.
go back to reference Hauschke D, Steinijans VW, Diletti E, Burke M. Sample size determination for bioequivalence assessment using a multiplicative model. J Pharmacokin Biopharm. 1992;20:557–61.CrossRef Hauschke D, Steinijans VW, Diletti E, Burke M. Sample size determination for bioequivalence assessment using a multiplicative model. J Pharmacokin Biopharm. 1992;20:557–61.CrossRef
18.
go back to reference Prueksaritanont T, Chu X, Gibson C, Cui D, Yee KL, Ballard J, Cabalu T, Hochman J. Drug-drug interaction studies: regulatory guidance and an industry perspective. AAPS J. 2013;15:629–45.CrossRefPubMedPubMedCentral Prueksaritanont T, Chu X, Gibson C, Cui D, Yee KL, Ballard J, Cabalu T, Hochman J. Drug-drug interaction studies: regulatory guidance and an industry perspective. AAPS J. 2013;15:629–45.CrossRefPubMedPubMedCentral
19.
go back to reference la Porte CJL, Back D, Blaschke T, Boucher CAB, Fletcher CV, Flexner C, et al. Updated guideline to perform therapeutic drug monitoring for antiretroviral agents. Rev Antivir Ther. 2006;3:4–14. la Porte CJL, Back D, Blaschke T, Boucher CAB, Fletcher CV, Flexner C, et al. Updated guideline to perform therapeutic drug monitoring for antiretroviral agents. Rev Antivir Ther. 2006;3:4–14.
20.
go back to reference Ahmmed SKM, Mukherjee PK, Bahadur S, Kar A, Al-Dhabi NA, Duraipandiyan V. Inhibition potential of Moringa oleifera Lam. on drug metabolizing enzymes. Indian J Tradit Know. 2015;14:614–9. Ahmmed SKM, Mukherjee PK, Bahadur S, Kar A, Al-Dhabi NA, Duraipandiyan V. Inhibition potential of Moringa oleifera Lam. on drug metabolizing enzymes. Indian J Tradit Know. 2015;14:614–9.
21.
go back to reference Davit B, Reynolds K, Yuan R, Ajayi F, Conner D, Fadiran E, et al. FDA Evaluations using in vitro metabolism to predict and interpret in vivo metabolic drug-drug interactions: impact on labeling. J Clin Pharmacol. 1999;39:899–910.CrossRefPubMed Davit B, Reynolds K, Yuan R, Ajayi F, Conner D, Fadiran E, et al. FDA Evaluations using in vitro metabolism to predict and interpret in vivo metabolic drug-drug interactions: impact on labeling. J Clin Pharmacol. 1999;39:899–910.CrossRefPubMed
22.
go back to reference Erickson DA, Mather G, Trager WF, Levy RH, Kearns JJ. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999;27:1488–95.PubMed Erickson DA, Mather G, Trager WF, Levy RH, Kearns JJ. Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos. 1999;27:1488–95.PubMed
23.
go back to reference Isoherranen N, Lutz JD, Chung SP, Hachad H, Levy RH, Ragueneau-Majlessi I. Importance of multi-P450 inhibition in drug-drug interactions: evaluation of incidence, inhibition magnitude and prediction from in vitro data. Chem Res Toxicol. 2012;25:2285–300.CrossRefPubMedPubMedCentral Isoherranen N, Lutz JD, Chung SP, Hachad H, Levy RH, Ragueneau-Majlessi I. Importance of multi-P450 inhibition in drug-drug interactions: evaluation of incidence, inhibition magnitude and prediction from in vitro data. Chem Res Toxicol. 2012;25:2285–300.CrossRefPubMedPubMedCentral
24.
go back to reference Stohs SJ, Hartman MJ. Review of the safety and efficacy of Moringa oleifera. Phytother Res. 2015;29:796–804.CrossRefPubMed Stohs SJ, Hartman MJ. Review of the safety and efficacy of Moringa oleifera. Phytother Res. 2015;29:796–804.CrossRefPubMed
25.
go back to reference Kappelhoff BS, van Leth F, Robinson PA, MacGregor TR, Baraldi E, Montella F, et al. Are adverse events of nevirapine and efavirenz related to plasma concentrations? Antivir Ther. 2005;10:489–98.PubMed Kappelhoff BS, van Leth F, Robinson PA, MacGregor TR, Baraldi E, Montella F, et al. Are adverse events of nevirapine and efavirenz related to plasma concentrations? Antivir Ther. 2005;10:489–98.PubMed
26.
go back to reference Wakeham K, Parkes-Ratanshi R, Watson V, Ggayi AB, Khoo S, Lalloo DG. Co-administration of fluconazole increases nevirapine concentrations in HIV-infected Ugandans. J Antimicrob Chemother. 2010;65:316–9.CrossRefPubMed Wakeham K, Parkes-Ratanshi R, Watson V, Ggayi AB, Khoo S, Lalloo DG. Co-administration of fluconazole increases nevirapine concentrations in HIV-infected Ugandans. J Antimicrob Chemother. 2010;65:316–9.CrossRefPubMed
27.
go back to reference Wang J, Kou H, Fu Q, Han Y, Qiu Z, Zuo L, et al. Nevirapine plasma concentrations are associated with virologic response and hepatotoxicity in Chinese patients with HIV infection. PLoS ONE. 2011. doi:10.1371/journal.pone.0026739. Wang J, Kou H, Fu Q, Han Y, Qiu Z, Zuo L, et al. Nevirapine plasma concentrations are associated with virologic response and hepatotoxicity in Chinese patients with HIV infection. PLoS ONE. 2011. doi:10.​1371/​journal.​pone.​0026739.
28.
go back to reference Ratanasuwan W, Jariyasethpong T, Anekthananon T, Intalapaporn P, Kongpatanakul S, Pongnarin P, et al. Association of nevirapine levels with rash or hepatotoxicity among HIV-infected Thai women. Open AIDS J. 2012;6:266–73.CrossRefPubMedPubMedCentral Ratanasuwan W, Jariyasethpong T, Anekthananon T, Intalapaporn P, Kongpatanakul S, Pongnarin P, et al. Association of nevirapine levels with rash or hepatotoxicity among HIV-infected Thai women. Open AIDS J. 2012;6:266–73.CrossRefPubMedPubMedCentral
Metadata
Title
Effect of Moringa oleifera Lam. leaf powder on the pharmacokinetics of nevirapine in HIV-infected adults: a one sequence cross-over study
Authors
Tsitsi G. Monera-Penduka
Charles C. Maponga
Alan R. Wolfe
Lubbe Wiesner
Gene D. Morse
Charles F. B. Nhachi
Publication date
01-12-2017
Publisher
BioMed Central
Published in
AIDS Research and Therapy / Issue 1/2017
Electronic ISSN: 1742-6405
DOI
https://doi.org/10.1186/s12981-017-0140-4

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