Patients on anti-retroviral (ARV) drug treatment are sometimes simultaneously taking other
prescribed drugs and/or over-the-counter drugs and/or herbal remedies. Pharmacokinetic
drug-drug or herb-drug interactions can occur in these patients, which might be synergistic
or antagonistic in nature leading to increased or decreased bioavailability of the ARV.
Consequences of bioavailability changes may either be adverse effects due to increased
plasma levels, or lack of pharmacological responses due to decreased plasma levels. The
aim of this study is to determine if pharmacokinetic interactions exist between selected
commercially available herbal products, namely Linctagon Forte®, Viral Choice® and
Canova® and the ARV, indinavir, in terms of transport and metabolism in cell culture models.
Bi-directional transport of indinavir was evaluated across Caco-2 cell monolayers in four
experimental groups, namely indinavir alone (200 μM, negative control group), indinavir in
combination with Linctagon Forte®, indinavir in combination with Viral Choice® and indinavir
in combination with Canova® at three different concentrations. Verapamil (100 μM), a known
P-gp inhibitor, was combined with indinavir in the positive control group. Samples obtained
from the transport studies were analysed by means of a validated high performance liquid
chromatography (HPLC) method. The apparent permeability coefficient (Papp) values were
calculated from the transport results in both directions and the efflux ratio (ER) values were
calculated from these Papp values. The metabolism of indinavir was determined in LS180
cells in the same groups as mentioned for the transport study but with ketoconazole (40 μM),
a known CYP3A4 inhibitor, as the positive control group. Indinavir and its predominant
metabolite (M6) were analysed in the metabolism samples by means of liquid
chromatography linked to mass spectroscopy (LC/MS/MS) to determine the effect of the
herbal products on the biotransformation of indinavir.
The BL-AP transport of indinavir increased in a concentration dependent way in the
presence of Linctagon Forte® and Viral Choice® when compared to that of indinavir alone
(control group). Canova® only slightly affected the efflux of indinavir compared to that of the
control group. Noticeable increases in the efflux ratio values of indinavir were found for
Linctagon Forte® and Viral Choice®, whilst the effect of Canova® on the efflux ratio value was
negligible.
There was a pronounced inhibition of the metabolism of indinavir in LS180 cells over the
entire concentration range for all the herbal products investigated in this study. These in
vitro pharmacokinetic interactions indicate the selected herbal products may affect indinavir’s bioavailability, but the clinical significance needs to be confirmed with in vivo studies before
final conclusions can be made. / MSc (Pharmaceutics), North-West University, Potchefstroom Campus, 2015
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:nwu/oai:dspace.nwu.ac.za:10394/14481 |
| Date | January 2014 |
| Creators | Calitz, Carlemi |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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