A critical review of the probable reasons for the poor/variable bioavailability of rifampicin from anti-tubercular fixed-dose combination (FDC) products, and the likely solutions to the problem

The problem or poor/variable bioavailability or rifampicin. which is shown in particular when the drugs are present in anti-tubercular fixed-dose comb ination (FDC) products, is a matter of serious concern. There is a potentia l of failure of therapy in patients with Lin active disease. It perhaps als o is a contributory factor towards the increasing resistance to anti-tuberc ular drugs. Unfortunately, the origin and cause of the problem is not clear ly understood, though GMP and crystalline changes in the drug are invariabl y cited as the principal reasons, In this write-up, various probable physic al and/or chemical reasons are critically reviewed. The enhanced decomposit ion of rifampicin in the presence of isoniazid in stomach after ingestion i s indicated to be the key factor behind the problem. Some simple solutions offered by the knowledge of the cause are discussed and it is concluded tha t there is a need to have a multifaceted approach to handle the problem. (C ) 2001 Elsevier Science B.V. All rights reserved.