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

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

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).

Keywords: HIV; Moringa oleifera; Nevirapine; Pharmacokinetics.

Figures

Fig. 1
Fig. 1
Mean nevirapine plasma concentration–time profile with and without moringa. The error bars represent the standard error of the mean
Fig. 2
Fig. 2
Individual AUC 0–12 of nevirapine with and without moringa. All patients maintained therapeutic plasma concentrations (>3.0 µg/mL) 12 h post-dose [19]
Fig. 3
Fig. 3
Individual Cmax,ss of nevirapine with and without moringa. All patients maintained therapeutic plasma concentrations (>3.0 µg/mL) 12 h post-dose [19]
Fig. 4
Fig. 4
Individual C12 of nevirapine with and without moringa. All patients maintained therapeutic plasma concentrations (>3.0 µg/mL) 12 h post-dose [19]

References

    1. 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. doi: 10.2174/1389200216666150223152348.
    1. Cho HJ, Yoon IS. Pharmacokinetic interactions of herbs with cytochrome p450 and p-glycoprotein. Evid Based Complement Altern Med. 2015
    1. Müller AC, Kanfer I. Potential pharmacokinetic interactions between antiretrovirals and medicinal plants used as complementary and African traditional medicines. Biopharm Drug Dispos. 2011;32:458–470. doi: 10.1002/bdd.775.
    1. 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. doi: 10.1080/03602530600754065.
    1. 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;2:379–383. doi: 10.3855/jidc.201.
    1. 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;3:22–24. doi: 10.4081/jphia.2012.e22.
    1. Popoola JO, Obembe OO. Local knowledge, use pattern and geographical distribution of Moringa oleifera Lam. (Moringaceae) in Nigeria. J Ethnopharmacol. 2013;150:682–691. doi: 10.1016/j.jep.2013.09.043.
    1. Taesotikul T, Navinpipatana V, Tassaneeyakul W. Selective inhibition of human cytochrome P450 1A2 by Moringa oleifera. Thai J Pharmacol. 2010;32:256–258.
    1. 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. doi: 10.2174/1872312808666140129123210.
    1. 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.
    1. 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;37:1557–1562. doi: 10.1124/dmd.108.024851.
    1. 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. doi: 10.1186/1471-2334-7-14.
    1. 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;15:420–421. doi: 10.1097/00002030-200102160-00019.
    1. Sauveur A, Broin M. Growing and processing moringa leaves. Moringa and Plant Resources Network 2010; .
    1. 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;7:84–88.
    1. Byakika-Tusiime J, Chinn LW, Oyugi JH, Obua C, Bangsberg DR, Kroetz DL. Steady state bioequivalence of generic and innovator formulations of stavudine, lamivudine, and nevirapine in HIV-infected Ugandan adults. PLoS ONE. 2008
    1. Hauschke D, Steinijans VW, Diletti E, Burke M. Sample size determination for bioequivalence assessment using a multiplicative model. J Pharmacokin Biopharm. 1992;20:557–561. doi: 10.1007/BF01061471.
    1. 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;15:629–645. doi: 10.1208/s12248-013-9470-x.
    1. 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.
    1. 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;14:614–619.
    1. 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. doi: 10.1177/00912709922008515.
    1. 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;27:1488–1495.
    1. 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;25:2285–2300. doi: 10.1021/tx300192g.
    1. Stohs SJ, Hartman MJ. Review of the safety and efficacy of Moringa oleifera. Phytother Res. 2015;29:796–804. doi: 10.1002/ptr.5325.
    1. 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;10:489–498.
    1. 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;65:316–319. doi: 10.1093/jac/dkp451.
    1. 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
    1. 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;6:266–273. doi: 10.2174/1874613601206010266.

Source: PubMed

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