| dc.description.abstract | Tuberculosis (TB) is a worldwide pandemic with vast challenges in the fight against the
disease. Challenges include the long and tedious treatment regimens and chemotherapy with
adverse side effects. One approach in defeating TB is to improve patient compliance to the
treatment regimes. The Pheroid™ drug delivery system possesses characteristics and abilities
to make it a good candidate to lower the dosage of the anti-TB actives; ethambutol (EMB),
rifampicin (RMP), pyrazinamide (PZA) and isoniazid (INH).
For the purpose of this study, the bioavailability of the anti-TB actives EMB, PZA, RMP and INH
were determined in the mouse model. Plasma was collected from 8 mice per group over 4
hours and analysed by an independent laboratory. Area under the plasma curve, as a function
of bioavailability, increased by 85.7% for EMB, 45.5% for INH and 33.2% for PZA with the
Pheroid™ formulation when compared with the formulation currently prescribed. Although not
significantly different, RMP also showed a 33.3% increase with the Pheroid™ formulation.
Bioavailability decreased between 7% and 58% for EMB, INH, and PZA when the formulation
currently prescribed is compared with the pro-Pheroid™ formulation, but RMP increased
significantly by 84%.
Efficacy of a Pheroid™ based formulation was compared to the free actives in the mouse
model. Mice were inoculated with Mycobacterium tuberculosis H37Rv reference strain.
Treatment started two weeks after inoculation and continued for 12 weeks with a 3 month post
treatment observation period. Methods used to assess treatment efficacy were the
Mycobacteria Growth Indicator Tubes (MGID method in parallel with a method counting colony
forming units (CFU) on agar plates. According to the MGIT method, the Pheroid™ treatment is
statistically more effective at week 4 by 10% and at week 10 by 9%. Although not statistically
more efficient, the Pheroid™ based treatment is 16.7% more effective at 3 months post
treatment. According to the agar plate method, the Pheroid™ treatment is statistically 7% more
effective than the Free drug treatment at week 2. Although the two methods gave slightly
different results, a trend in efficacy could be observed. The mice treated with the Pheroid™
formulations showed a significant improvement from onset of treatment to about week 10 (with
the exception of week 6) and again at 3 months post treatment.
The bioavailability and efficacy data accumulated in this study indicate that a new antituberculosis
treatment regime based on the Pheroid™ drug delivery system opens the
opportunity for a new dosage form where APls are either lowered, treatment time shortened or
treatment intervals increased. TB patient compliance might be improved with such a new
treatment regime while assisting in the fight against TB. | |
