If the latest studies on the anti-TB combination therapy are to be relied, the bioavailability of rifampicin, the key drug that attacks tuberculosis bacteria in the two and three drug combinations of rifampicin-isoniazid, is impaired to the extent of almost 50 per cent. Although the existing WHO guideline for anti-TB drugs has taken care of the currently established mild rifampicin loss in the INH (isoniazid) combination, the new revelation by the eminent scientist Prof. Arnold H Becket, who is presently working on this anti-TB drug pharmacology, points out to a drastic impact of spreading drug resistant tuberculosis while continuing with this irrational therapy.
Prof. Becket, the internationally acclaimed pharma scientist and expert in drug dissolution, revealed this while talking about his new findings regarding rifampicin-isnoiazid reaction while combined in therapy, in an exclusive interview with Pharmabiz in Mumbai. "This is very unfortunate that neither the manufacturers nor the government of India has moved towards rectifying the error by analysing the actual bioavailability of these combinations or to ensure the bioequivalence of such products allowed for marketing," he said.
Apart from this, since the current dosage of rifampicin in this combination varies from product to product, the commercial implications on both the manufacturer and patients are high. Though there exists WHO guideline on the bioavailability testing and dosage fixing etc. for anti-TB drugs, there are no uniform practices followed by manufacturers in India. India currently produces the largest volume of anti-TB formulations also the country is one of the largest TB affected regions in the world.
As no serious efforts are on into the development of new drugs or new technology by the industry, the scenario remains the same for a long time and the government agencies are yet to come out publicly to address the issue. As the patient compliance is an important factor in the success of the treatment, the WHO has recommended combination therapy. At present, combinations of rifampicin with drugs like isoniazid, Ethambutol and pyrazinamide are allowed in the country and a number of big and small companies are manufacturing and marketing these brands.
There were studies conducted by reputed institutions like National Pharmaceutical Education and Research (NIPER) and also by a host of individual drug experts on the impaired bioavailability of rifampicin-isoniazid combination. As the drugs react each other in the acidic stomach conditions, there is a clear degradation of rifampicin bioavailability. The NIPER had admitted that the rifampicin loss due to INH reaction is around 20 per cent. However, a group of manufacturers are claiming that the adequate bioavailability is being taken care of while fixing the dosage of rifampicin whereas another group is arguing that there is no clinical relevance for the degradation as the results of bioavailability test and dissolution tests are not always the same.
However, the latest findings have contradicted both the arguments. Prof Arnold's findings show that since the rifampicin loss is such high in the INH combination, it will have definite clinical relevance. Hence the solution here is either to disallow the rifampicin-INH combination or to have technology for separated dissolution of these drugs in the body.
Of late, there are few companies in India, which have developed a new disintegration technology for adequate bioavailability of rifampicin, but the uncertainty on the economic viability of the final product has delayed the introduction of the product in the market. And certainly, there are no attempts in advanced countries and by multinationals towards this, as anti-tuberculosis products have not been considered as priority or money-spinners for them.