Chapter 1:

1.0 Background

Over the past decade, a number of herbal and complimentary products has 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.

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. 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. 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 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. 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. 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. 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. 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.