Simulation of metabolism-based herb-drug interaction: towards safe and efficacious use of NIPRD-AM1

Document Type : Short communication

Authors

1 Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development, PMB 21, Abuja, Nigeria

2 Department of Medicinal Chemistry and Quality Control, National Institute for Pharmaceutical Research and Development, PMB 21, Abuja, Nigeria

3 African Institute of Biomedical Science and Technology (AiBST), Cnr Chinhoyi Str./Jason Moyo Ave. No. 9 at LAPF Centre, Harare, Zimbabwe

4 Director General/Chief Executive Officer, National Institute for Pharmaceutical Research and Development, PMB 21, Abuja, Nigeria

Abstract

Objective: To evaluate the effect of NIPRD-AM1 on CYP3A4 in order to generate clinically significant data for its safe and efficacious use.
Materials and Methods: NIPRD-AM1 is a phytomedicine developed from aqueous root extracts of Nauclea latifolia Smith (Rubiaceae) for the treatment of uncomplicated malaria. The effect of NIPRD-AM1 on CYP3A4 was measured with and without the addition of NIPRD-AM1, by testing different concentrations of the product at 37 °C in reactive mixtures with ketoconazole (2.5 µM) as the positive control.
Results: Results showed a very low IC50 value of 0.01 mg/ml similar to that of ketoconazole (0.016 mg/ml).
Conclusion: Metabolic processes of NIPRD-AM1 are likely to inhibit CYP3A4, with potential implication on drugs that are CYP3A4 substrates. This is a promising approach for guidance towards the safe and efficacious use of NIPRD-AM1.

Keywords


Abbah J, Amos S, Chindo B, Ngazal I, Vongtau HO, Adzu B, Farida T, Odutola AA, Wambebe C, Gamaniel KS. 2010. Pharmacological evidence favouring the use of Nauclea latifolia in malaria ethnopharmacy. J Ethnopharmacol, 127: 85-90.
Ameh S, Obodozie O, Gamaniel S, Abubakar M, Garba M. 2010. Physicochemical variables and     real time stability of the herbal substance of Niprd-AM1®-an antimalarial developed from   the root of Nauclea latifolia S.M. (Rubiaceae). Int J Phytomed, 2: 332-340.
Amos S, Abbah J, Binda L, Adzu B, Buhari S, Odutola AA, Wambebe C, Gamaniel K. 2005. Neuropharmacological effects of the aqueous extract of Nauclea latifolia root bark in rats and mice. J Ethnopharmacol, 97: 53-57.
Evans WE, Relling MV. 1999. Pharmacogenomics: translating functional genomics into rational therapeutics. Science, 286: 487-491.
Fugh-Berman A. 2000. Herb-drug interactions. The Lancet, 355: 134-138.
Gamaniel K, Wambebe C, Amupitan J, Hussaini IM, Amos S, Awodogan MO, Usman H, Enwerem N. 1997. Active column fractions of Nauclea latifolia on Plasmodium berghei on rabbit ileum. J Pharm Res Dev, 2: 44-47.
Gamaniel K. 2008. A comparative randomized clinical trial of NIPRD-AM1 against a chloroquine and sulphodoxine pyrimethamine combination in symptomatic but uncomplicated malaria. Abstract of the World Congress on Medicinal and Aromatic      Plants, Cape Town, Nov. 2008.
Gwaza L, Wolfe AR, Benet LZ, Guglielmo BJ, Chagwera TE, Maponga CC, Masimirembwa CM. 2009. In vitro inhibitory effects of Hypoxis obtuse and Dicoma anomala on cyp450 enzymes and p-glycoprotein. Afr J Phar Pharmacol, 3: 539-546.
Nerbert DW, Russell DW. 2002. Clinical importance of the cytochromes p450. The Lancet, 360:     1155-1162.
Monera TG, Wolfe AR, Maponga CC, Benet LZ, Guglielmo J. 2008. Moringa oleifera leaf extracts inhibit 6-hydroxylation of testosterone by CYP3A4. J Infect Dev Ctries, 2: 379-383.
Wienkers LC, Heath TG. 2005. Predicting the in vivo drug interactions from in vitro drug discovery data. Nat Rev Drug Disc, 4: 825-833.