Correlation between steady-state plasma concentration of antituberculous drugs and age, inclusion of rifampicin in the treatment regimen, adverse drug reactions and other clinical parameters

A regional hospital in Hong Kong examined the correlation between plasma concentrations of rifampicin, pyrazinamide, isoniazid and its metabolite hydrazine and age, inclusion of rifampicin in the treatment regimen, adverse drug reactions and other clinical parameters. One hundred eighty subjects with tuberculosis were admitted consecutively to the medical wards of the Prince of Wales Hospital over a one and a half year period. Elderly patients > 65 years were randomized into one of two treatments with and without rifampicin in addition to isoniazid, pyrazinamide and ethambutol; younger patients received all four drugs. Plasma antituberculous drug concentrations were determined using high performance liquid chromatography. Elderly patients taking rifampicin had a higher mean steady-state concentration of isoniazid, together with a higher incidence of adverse effects compared with those not taking rifampicin. No age related differences were observed for the other drugs. For the whole group, higher mean concentrations of hydrazine, rifampicin and pyrazinamide were associated with a higher incidence of adverse effects and the presence of coexisting diseases. It is concluded that in sick elderly patients with coexisting diseases, use of rifampicin in the antituberculous regimen should be accompanied by close monitoring for side effects, and that there may be an indication for use of lower dosages of antituberculous drugs in such patients.