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The optimization of the therapy of lung tuberculosis and asthma bronchiale was supported since 1955 by clinical-pharmacological investigations. The prerequisites therefore--using highly specific methods of distribution and quantification in biological material till to the synthesis of 3H-INH and 3H-RMP were introduced step by step. The investigations--in most cases estimations of the nonbiotransformated part of antituberculotic drugs and theophylline had following purposes: security of the necessary dose especially in the case of INH (hereditary INH-polymorphismus), proof of a sufficient permeation of INH and RMP in the tuberculous kidney, control of the usefulness or uselessness of the INH-depot-preparations, relations between the concentration in the serum and dose respectively of the appearance of side effects, estimation of bioavailability and pharmacokinetic parameters during the development of an useful retard-preparation of theophylline.

With a rifampicin (RMP) range of 600 to 1800 mg, 12.5% of the administered dose are on an average secreted in urine. In spite of this minimal portion the course of pharmacokinetic processes can distinctly be learned from its alterations. Analyses in 84 patients revealed that the age will influence the induction and the sex-specific differences of the pharmacokinetics. Compared to male subjects, an increased RMP secretion in urine can be recorded in young female subjects, whereas in older male ones an induction-reduced RMP elimination in urine becomes more obviously. Considering these multiform processes, the determination of the bioavailability of RMP preparations by means of the RMP secretion in urine is taken to be manipulatable and uncertainly. More evident results can be gained by the determination of the RMP concentration in serum or by the calculation of the AUC.

Pharmacokinetic investigations in 75 patients receiving their first treatment for infectious lung tuberculosis gave the following results: RMP and its products of biotransformation are excreted via the urine in smaller amounts in patients above 55 years than in younger patients. In the older age group the induction phase - as measured by the urinary excretion of RMP - is also more marked than in younger patients. Both the serum RMP-concentration and the urinary excretion of RMP are significantly higher in women than in men. The sex specific differences in pharacokinetics seem to be of clinical importance. Because of the higher serum RMP-concentration it is possible to reduce the RMP-dosage 10% in female patients, even with intermittent administration, and to diminish the risk of dose-dependent side effects.