Chapter 1:

1.0 Background

Over the past decade, a number of herbal and complimentary products have attracted

growing as an alternative for the prevention, mitigation and treatment of various

diseases. Due to the high frequency of using herbal medicines, the concurrent use of

herbal medicines and conventional drugs has also increased. Although herbal products

are generally regarded as safe, however some of their constituents can modify

countless xenobiotic metabolic reactions and transport systems which play an important

role in absorption and distribution of conventional prescription drugs. Concurrent use of

herbal and complimentary medicines increases the chances of interactions between

drug metabolic enzymes and herbal constituents as well as drug transporters with

herbal constituents which can alter the pharmacokinetics of the conventional drugs. For

example, the constituent in Allium cepa (onion), quercetin inhibits the activity of human

CYP3A4 cytochrome enzyme and P-gp-mediated efflux of ritonavir in cells (Cho and

Yoon, 2014).

With more and more popular use of herbal medicines, herb-drug interactions have

become an increasingly safety issue in the clinical application of conventional drugs

(Dejun and Lifeng, 2011). A drug interaction is a change in the action or side effects of a

drug caused by concomitant administration with a food, beverage, herb or another drug

(Viera and Huang, 2012). These are complicated due to the fact that multiple chemical

components are involved and these components possess diverse pharmacological

activities.Drug interactions occur when one chemical or substance affects the way in
which another drug is absorbed, distributed, metabolized and eliminated from the

system (Bakare-Odunola et al. 2008). Herbs may affect the behavior of the

concomitantly used drugs by changing their absorption, distribution, metabolism and

excretion which potentially cause changes in drug levels and activity leading to either

therapeutic failure or toxicity. Also, there may be unquantified interactions between

conventional drugs and herbal medicines (Koury 2003).

Biotransformation reactions can be classified into two phases, phase I reactions and

phase II reactions. Phase I reactions (functionalization) involves the introduction or

generation or exposure of hydrophilic groups of the metabolite. Phase II reactions

(conjugation) involve the conjugation of an endogenous radical to the drug metabolite.

Phase I metabolic reactions include oxidation, reduction and hydrolysis and these are

catalyzed by cytochrome P-450. Biotransformation reactions can be classified into two

i.e. phase I reactions and phase II reactions. Phase I reactions (functionalization)

involves the introduction or generation or exposure of hydrophilic groups of the

metabolite. Phase II reactions (conjugation) involve the conjugation of an endogenous

radical to the drug metabolite. Phase I metabolic reactions include oxidation, reduction

and hydrolysis and these are catalyzed by cytochrome P-450 isoenzymes. These are a

super family of enzymes which are commonly known as microsomal mixed function

oxidases which are responsible for catalyzing the bio-inorganic chemistry of drug

metabolism. A bulk of all commonly prescribed conventional drugs is metabolized by the

cytochrome p450 isoenzymes (Taxak and Bharatam, 2014). P-glycoprotein is an ATP-

dependent efflux pump which plays a significant role in the intestinal absorption and

distribution to the central nervous system and also in the urinary extraction of drugs.
Therefore, the inhibition or induction of CYP isoenzymes and P-glycoprotein by

concurrent use of herbs may result in pharmacokinetic interactions resulting in

fluctuations in the plasma concentrations of drugs. Pharmacokinetic studies have to be

carried out so as to determine the side effects profiles as well as identify drug-herbal

combinations that pose risks (Mustapha et al. 2009).

1.1 Problem statement

In the past ten years, the popularity of herbal medicines has become an increasingly

important in the medical field (Elliot, 2019). These medicines are generally regarded as

safe but concurrently administration of these herbal medicines and conventional

medicines has become a serious clinical issue. Many adverse effects occur because

are mostly used by an increasingly number of patients who do not adverse their

clinicians of concomitant use leading to potentially harmful drug-herb interactions (Adzu

et al, 2001). In response to the aforementioned problem, this study proposes to carry

out research on the pharmacokinetic effects of using concurrently using ginger and oral

paracetamol. This therefore not only addresses a knowledge gap but also helps in

curbing the clinical problem of drug-herb interactions.

1.2 Aim

To investigate the effects of water extracts of ginger on the single oral dose

pharmacokinetics of paracetamol in rats

1.3 Objectives

1. To extract the phytoconstituents in the Zingiber officinale plant.

 2. To orally administer oral paracetamol alone in one group of albino rats and to

another group a combination with the Zingiber officinale extract.

3. To withdraw blood from the marginal veins of the rats

4. To measure the plasma concentration of Acetaminophen by the method

described by Ofeufule et al.

5. To analyze the results of the investigation by means of statistical inferences.

1.4 Justification.

The purpose of this project is to carry out pharmacokinetic interaction studies in patients

concurrently taking herbal Ginger and paracetamol. Although drug-drug interactions

have been extensively studied, many reports on the drug-herb interactions are sketchy

and lack analysis of suspect preparations, hence there is a need to study the

pharmacokinetic effects of herbs on conventional drugs in order to fill an academic gap.

There is a recent increase of adoption of complementary and alternative medicines by

society as patients believe that they are safer and more effective than conventional

medicines (Saad et al, 2005). This high frequency of using herbal medicines has also

caused an upsurge in the concurrent use of both conventional and herbal medicines.

This project aims to carry out pharmacokinetic studies between a herbal medicine and a

conventional drug used concurrently in order to determine if the combination poses risks

or is beneficial (Bakare-Odunola et al, 2010). The results of this investigation may

provide an insight of how medical practitioners and patients can help to curb the

dangers of drug-herb interactions which is a serious clinical problem.