Pharmacokinetic Interactions between Bioenhancers of Herbal Origin and Antiretroviral Drugs using Cytochrome P450 3A Inhibition Approach.
Abstract
The co-administration of oral therapeutic agents with natural compounds is currently on the increase with resultant increase in herb-drug interaction cases involving mainly cytochrome P450 enzymes and drug transporters.
HIV infection because of its chronic and comorbid nature often necessitate the use of multiple drugs including herbs to relief symptoms.
Meanwhile, most natural products have been shown to modulate drug metabolising enzymes, resulting in alteration in co-administered drug concentrations.
The aims of this study therefore, were to evaluate the in vitro and in vivo effects of some identified herb extracts used by HIV-infected patients on liver and intestinal cytochrome P450 3A enzymes and also to determine the extracts pretreatment effect on the bioavailability of some antiretroviral agents.
The study adopted both survey and exprimental designs.A cross sectional study was conducted in HIV clinic using a 25-item adapted questionnaire to identify the prevalence and pattern of herbal drug use among HIV infected patients on antiretroviral therapy.
Some of the identified herbs were collected and extracted using aqueous and non-aqueous solvents and concentrated using lyophilizer and rotary evaporator respectively.
In vitro inhibition of the cytochrome P450 3A enzymes by the extracts were assessed in liver and intestinal microsomes using erythromycin-N-demethylation assay (EMND) method while their in vivo effects were determined by estimating simvastatin (CYP3A probe substrate) plasma concentrations in female rate model.
The effect of the extracts on two antiretroviral agents’ pharmacokinetics were determined by the administrations of the drug and the extracts to different rats divided into different groups of 5 rats per group and their plasma drug concentrations determined at different time intervals using HPLC.
Pharmacokinetic parameters were determined using non-compartmental anaysis as implemented in WinNonlin pharmacokineticsoftware application.
The effects of the extracts and the antiretroviral agents, administered concurrently, on hematological and biochemical parameters were determined.
HPLC fingerprinting assay was done to determine the extracts chemical constituents. All results were presented as mean±SEM.
The data were subjected to one-way analysis of variance (ANOVA) test and group differences determined using post hoc test (LSD) using SPSS. Results were considered statistically significant at P<0.05.
Introduction
Background Of Study
Until recently, all medicines were derived from natural materials (Sionneau & Pao, 1995) including those from earth, plant and animal origins.
Herbal medicines paved way for the conventional medicine with most drugs used in orthodox medicine originally derived from plant and animal materials.
The term herb/herbal products is commonly used for all preparations obtained from herbs, spices, roots, leaves and other non-botanical materials of natural origin (Obodozie, 2012).
Although, its name and natural source suggests something that is beneficial and has little potential for harm, numerous toxic materials, such as foxglove, deadly nightshade and jimson weed (datura), have been known.
However, practitioners sometimes process the herbs to change them from their original form (Darling, 2002), and even isolate some active constituents, so that the end products are often not as nature presented them may be to reduce or abolish the toxicity.
For example, aconite was processed extensively in China to reduce its toxicity so that it could readily be used, and borneol, the active constituent found in a few tropical plants, was isolated centuries ago in relatively pure form, for both internal and external use (Leake, 1975).
Herbal medicine therefore, refers to all preparations gotten from herbs, spices, roots, stems, leaves and other non-botanical materials of natural origin which can be used for its therapeutic purposes.
These preparations may be used either as topical agents or for internal use. Herbal medicine is an integral part of Traditional medicine which has been defined by the World Health Organization (WHO) as the total of the knowledge, skills, and practices based on the theories.
Beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illness (WHO, n.d.).
The World Health Organization’s estimate that 65-80 % of the population in developing countries relies on herbal medicines as primary source of treatment (Rahman & Singhal, 2002), points to the importance of this form of medicine.
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