Serum rifampicin concentration related to dose size and to the incidence of the ‘flu’ syndrome during intermittent rifampicin administration

Abstract

In Hong Kong 116 patients and in Singapore 232 patients with pulmonary tuberculosis were treated with once-weekly antituberculosis regimens containing rifampicin in mean dosages of 23.3 mg/kg body weight in Hong Kong and of 21.5 and 13.7 mg/kg in Singapore. Half the patients, at random, were given, double-blind, a daily supplement of rifampicin 75 mg in Hong Kong and 25 mg in Singapore. The 3 once-weekly dosages without the supplement were associated with an incidence of the ‘flu’ syndrome of 55, 24 and 11% with a geometric mean maximum serum rifampicin concentration of 23.7, 20.6 and 14.9 μg/ml, and with a mean integral of the product of concentration and time of 227.6, 192.8 and 121.3 μg/ml hours, respectively. The rifampicin supplement of 75 mg reduced the incidence of the ‘flu’ syndrome in the Hong Kong patients, but in Singapore the 25 mg supplement had no effect. These findings are discussed.