South African Traditional Medicines Research Unit
Current projects 9 - 10
- Pharmacokinetics
and pharmacodynamics of rectal artesunate in patients with moderately severe
or severe and complicated falciparum malaria in northern KwaZulu-Natal
Supervisor:
Prof. P.I. Folb
Principal Investigator: Dr Karen I. Barnes
The goal of this research
is to determine the pharmacokinetics and pharmacodynamics of artesunate suppositories
in 100 patients with moderately severe or severe falciparum malaria.
Specific objectives:
- To measure
- parasite clearance
time,
- plasma artesunate
and dihydro-artemisinin concentrations by HPLC at six specified time
points;
- plasma anti-malarial
bio-assay at the same six time points.
- To calculate
from these results the proportion of patients treated with rectal artesunate
who achieve an AUC greater than IC90 of artesunate and dihydro-artemisinin.
- To compare the kinetics
of intravenous quinine when administered as monotherapy with the kinetics
of intravenous quinine when combined with artesunate treatment, to assess
whether a pharmacokinetic drug interaction occurs in patients with severe
and complicated malaria.
- To compare the:
- fever clearance
rates;
- parasite clearance
rates;
- time to return
to per os status; and
- coma recovery times;
in patients treated with rectal artesunate with the rates of controls.
- In
vitro antimalarial activity of 24d and the chloroquine resistance reversing
effects of 3m on plasmodium falciparum
Project
Leaders: Prof. Peter Folb, Dr Peter Smith, Mr W. Campbell
Primary Investigator: Mr. Motlalepula Gilbert Matsabisa
Specific objectives:
- Development of a
phytochemical profile for the plants of interest by bioactivity-guided
characterisation;
- Standardisation of
the extraction protocol and stability testing of the extracts of 3M and
24D;
- Tests for reversal
of cancer resistance in order to assess whether the resistance reversal
properties noted are general or specific to the malaria parasite;
- Antimalarial testing
in vitro using drug-sensitive and drug-resistant parasites, and in vivo
testing using P. Berg;
- Animal toxicity testing;
The beneficiary of the
research grant will be Motlalepula Gilbert Matsabisa, whose research to
date has contributed significantly to the achievements thus far of this
project.
Under the supervision
of the principal investigator in the United Kingdom, Dr David Reid, at the
Analytical Sciences Department of SmithKline Beecham, Mr Matsabisa will
receive special training in a number of advanced analytical techniques.
These will include:
- mass spectrometry;
- high field (400 and
500 MHz) nuclear magnetic resonance;
- optical and vibrational
spectroscopic methods;
- separation techniques
like hplc, capillary electrophoresis, chiral chromatography, LC-MS and
LC-NMR.
Mr Matsabisa will be
able to transfer the benefits of his training to the laboratories at the
Department of Pharmacology at the University of the Cape Town. This will
entail a substantial transfer of technology and we expect that Mr Matsabisa
will be in a position to assume a leadership role in medical scientific
work at the end of his research training, which will take another two to
three years.
Outcomes
The following outputs will be obtained as a result of this work:
- PhD thesis - G Matsabisa
- Two to three seminal
articles dealing with novel traditional medicines used to combat malaria,
including the reversal of drug resistance in Plasmodium falciparum;
- Three to four honours
students will be trained in the same research methodology over the same
period (at least one of these, and probably both, will have come from
a disadvantaged background);
- Three masters students
will be trained in the same methodology.
|
