Download WAHOME EPHANTUS KARIUKI

1.0 INTRODUCTION
Mycobacteria readily develop resistance to most antimicrobials .Mycobacterial cells can also be dormant
and some undergo encapsulation thus completely resistant to many drugs or killed only very slowly.
Combinations of two or more drugs are required to overcome challenges as the lipid-rich mycobacterial
cell is impermeable to many agents (11). Mycobacterial cells are intracellular pathogens and they
develop resistance as a result of inappropriate drug selection and use of monotherapy (27).
The introduction of FDCs formulations in the national programs is limited by possible bioequivalency of
rifampicin if present in FDC form. In this regard WHO and IVATLD recommend FDCs of proven rifampicin
bioavaoilability .Bioequivalence studies of both rifampicin and isoniazid shows that in vitro interaction of
rifampicin is clinically insignificant. Thus it was concluded that FDC formulation is bioequivalent for
rifampicin, isoniazid and pyrazinamide and ensures treatment of TB without compromising efficacy of
any of these components of anti-TB therapy (8). This may due to development of a gastro retentive
modified release RIF tablet and an enteric coated isoniazid capsule(2 tablets of RIF and 1capsule of INH
put into a hard gelatin capsule) to minimize concentration dependent degradation of RIF in presence of
INH. This is a delivery system (novel solid dosage form) which releases RIF in the gastric medium and INH
in distal jejunum or ileum. (1)
Bioavailability (BA) is defined as the fraction of unchanged drug reaching systemic circulation following
administration by any route. Some factors affecting BA include gastric emptying rate, intestinal transit
time, hepatic first pass metabolism, gastrointestinal and hepatic blood flow, drug formulation, disease
conditions, diet, enzyme inhibition or induction by other drugs/foods, physical properties of drug ( e.g.
hydrophilicity, pka, solubility), interactions with other drugs or foods, transporters(e.g. p-glycoprotein),
individual variations in metabolism, health of GI tract, age, phenotypic differences, circadian differences
etc.(12)