Moringa Oleifera- Antiretroviral Pharmacokinetic Drug Interaction
Keywords
Abstract
Description
The use of herbal supplements is widespread in Africa, particularly for the management of HIV and AIDS. In Zimbabwe, the prevalence of herbal medicine use in HIV-infected people is as high as 79% (Sebit et al., 2000). Several studies have shown that the herb Moringa oleifera is among the top 10 herbs most commonly used by HIV-positive people in Zimbabwe (Makomeya et al 2004, Monera et al 2008). Another review also cited Moringa as one of the 53 most important African medicinal plants presently traded (van den Bout-van den Beukel et al 2006). Others included Hypoxis hemerocallidea (African potato) and Sutherlandia frutescens-(Cancer bush). Moringa is rich in β-carotene, protein, vitamin C, calcium and potassium and act as a good source of natural antioxidants (Anwar et al.,2007).It is recommended by non-governmental organisations and some African governments as an immune booster and a nutritional supplement for people living with HIV and AIDS (Ncube, 2006). Most advocates and users believe that since the herb is natural, it is free from all side effects and interactions.
Concomitant use of herbs with conventional drugs may lead to herb-drug interactions in the same way that two or more co-administered drugs may interact. Herbal constituents that are substrates for the same enzymes or transporters of conventional drugs may induce or inhibit the enzymes and/or transporter activity. Pharmacokinetic endpoints such as area under the curve (AUC), time to maximum plasma concentration (tmax), peak plasma concentration (Cmax), trough concentration (Cmin), clearance (CL), volume of distribution (Vd/F) and half-life (T1/2) may be altered significantly resulting in toxicity, more severe adverse effects, sub-therapeutic drug concentrations, HIV resistance and treatment failure.The risk of interaction increases as the number of co-administered drugs increases (de Maat et al 2003). As a result, people taking herbal medicines while on antiretroviral therapy are at very high risk because of the multitude use of highly active antiretroviral drugs and treatment of opportunistic infections, and also because herbs contain a wide range of bioactive chemical constituents.
However, evidence based information of such effects is usually lacking and as such; health practitioners' ability to make relevant clinical decisions is limited. Results of a review of in vitro studies suggest a need for in vivo metabolic drug-drug interaction studies (van den Bout-van den Beukel et al 2006). Preliminary in vivo studies in animal models can serve as a basis for clinical trials, the results of which are considered the gold standard in this era of evidence-based medicine.
Primary objectives
1. To compare the steady-state pharmacokinetics of nevirapine and efavirenz in HIV-positive patients before and after supplementation with Moringa oleifera leaf powder
2. To compare the single dose pharmacokinetics of nevirapine and efavirenz in rat models before and after supplementation with Moringa oleifera leaf powder
Secondary objectives
3. To determine the bioavailability of Moringa oleifera leaf powder in humans after oral dosing using beta carotene as a bio marker.
4. To compare urine chemistries and liver function tests in HIV patients before and after supplementation with Moringa oleifera leaf powder
5. To determine the presence of any genetic variation in the participants in the genes that code for CYP3A4 and CYP2B6
Dates
| Last Verified: | 02/28/2019 |
| First Submitted: | 08/02/2011 |
| Estimated Enrollment Submitted: | 08/02/2011 |
| First Posted: | 08/03/2011 |
| Last Update Submitted: | 03/28/2019 |
| Last Update Posted: | 04/01/2019 |
| Date of first submitted results: | 08/22/2017 |
| Date of first submitted QC results: | 03/28/2019 |
| Date of first posted results: | 04/01/2019 |
| Actual Study Start Date: | 12/31/2012 |
| Estimated Primary Completion Date: | 08/31/2013 |
| Estimated Study Completion Date: | 08/31/2013 |
Condition or disease
Intervention/treatment
Dietary Supplement: Moringa oleifera
Drug: Efavirenz
Drug: Nevirapine
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Nevirapine HIV positive patients on nevirapine containing regimen, taking Moringa oleifera leaf powder | Drug: Nevirapine Nevirapine 200mg based regimen |
| Efavirenz HIV positive patients on efavirenz containing regimen, taking Moringa oleifera | Drug: Efavirenz Efavirenz 600mg based regimen |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Sampling method | Probability Sample |
| Accepts Healthy Volunteers | Yes |
| Criteria | Inclusion Criteria: - HIV positive, - ≥ 4 weeks on Nevirapine or , ≥ 2 weeks on Efavirenz containing regimen, - Supplements HAART with Moringa oleifera. Exclusion Criteria: Known hepatic, intestinal or renal disease,smoking, chronic alcohol ingestion, poor venous access, chronic alcohol ingestion, pregnant, smoking, on rifampicin, ketoconazole, isoniazid, breastfeeding, anaemia,vomiting |
Outcome
Primary Outcome Measures
1. AUC [Baseline (day 22), Post-moringa (day 35)]
Secondary Outcome Measures
1. C12h [Baseline (Day 22); Post-moringa (Day 35)]
Other Outcome Measures
1. Cmax [Baseline (day 22), Post-moringa (day 35)]
