THE EFFECT OF VITAMIN C ON PHARMACOKINETIC PARAMETERS OF CHLOROQUINE IN HEALTHY HUMAN VOLUNTEERS

ABSTRACT

This study was undertaken to compare the effect of vitamin C on the pharmacokinetics of chloroquine using human volunteers. Quality control studies for both chloroquine and vitamin C; identification test, assay, weight variation, friability, disintegration time and dissolution rate were carried out according to BP 2009. Jayanathi et al., 1994 method was adopted and validated based on ICH guideline for this study. Calibration curve was constructed within the range of 2 – 10 µg/ml and validated. The adopted method was then employed in determining the effect of vitamin C on the pharmacokinetics parameters (Cmax, Tmax, Ka, Ke, t1/2a, t1/2e, Cl, Vd, lag time and AUC) of chloroquine using human volunteers of 30 years and above and the study was divided into three phases with a washout period of three weeks. Both chloroquine and vitamin C used for this study were found to have the labeled active ingredient. They all passed the assay test as they were within the acceptable limits 95 – 105 %. Weight variation was conducted for both chloroquine and vitamin C and they all passed as their percentage mean deviation was less than 5 %. Similarly, both drugs passed the friability test which was less than 1%. Disintegration tests for both drugs reveals that they disintegrate in less 5 mins and also both chloroquine and vitamin C passed the dissolution rate as more than 70 % of the active ingredient was released in 30 mins. The percentage recovery of the method was within the accepted range of 98 – 102 %. Calibration curve was linear within the range of 2 – 10 µg/ml as the correlation coefficient was 0.9905. The regression equation was y= 0.001x + 0.120. When chloroquine was administered alone no significant difference (p<0.05) at lower values was observed, however, on co-administration of chloroquine and vitamin C no significant difference (p<0.05) at lower values was also observed, except for clearance (Cl) which was statistically significant (p<0.05) at lower values. On the other hand, when an hour delayed administration of chloroquine and vitamin C no significant difference (p<0.05) was observed, except for clearance (Cl) which was also statistically significant (p<0.05) at lower values. This finding indicates that vitamin C may influence the pharmacokinetics of chloroquine when co-administered together depending on the time of administration of the two drugs.

CHAPTER ONE

1.0 INTRODUCTION

1.1 Drug interaction

It is evident that in some cases when two or more drugs are administered concurrently or at an interval of time, the expected pharmacological action is not being obtained. Sometimes potentiation of action of one of the drug may be observed. While on the other hand a diminished in action of the other drug occurs in some cases. This could be best explained through the study of possible interaction between the drugs in question. This is termed as drug – drug interaction study. (Pixtrim et al., 1995).

There are many ways in which drug administrated by any route may interact in the patient to produce a harmful effect. Some of these interactions occur only when two drugs are administered within hours, days or weeks of each other; and sometimes the interaction take place only after one of the drugs has been taken for several weeks. There are biochemical explanations for some of this interaction, but for others there is yet no information available about the basic mechanism involved.

1.1.1 General mechanism of action

The mechanism of drug interaction development can be best explained into 2 ways.

1.1.1.1 Pharmacokinetics interactions

A).     Absorption

b).      Distribution

c).         Elimination

1.1.1.2 Pharmacodynamics interactions

  1. Enhanced effect produced by 2 drugs acting at the same site.
  2. The increase effect produced by 2 drugs ‘at different receptors site.
  3. Enhanced effect of 2 drugs by one which is devoid of action itself.
  4. Antagonism of the effect of one drug by another.

Pharmacokinetics

Most of drugs interactions are kinetics in origin, one of the most useful pharmacokinetics concepts to have emerged in recent years particular in understanding interaction is that of the area inscribed by the plasma concentration. Time curve of a drug. After a single dose, this area (AUC) is a function of the dose, the fraction of the dose entering the general circulation and the drug clearance (Lappin et al., 2006)

This can be expressed as follows;

AUC = D x F/C———————— (1.1)

 

Where;

AUC = area under curve

D = dose

C = drug clearance

F = fraction of the dose entering the general circulation

When a drug is given repetitively, accumulation occurs and the plasma concentration increase after each dose until a steady state is reached provided that:

  1. Absorption is not altered.
  2. Drug binding to plasma proteins remains constant over a wide concentration range.
  3. Elimination rate is not dose dependent.
  4. The drug does not induced its metabolism, then
AUC (SD) = AUC (MD) ————————— (1.2)

 

AUC (SD) = Area under curve during’ single dose.

AUC (MD) = Area under curve during multiple dose.