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A specific direct method for determining the isoniazid derivative isonicotinoyl-hydrazine sodium glucuronide (INHG-Na) with the aid of high-pressure liquid chromatography has been developed, which permits the analysis of this derivative of isoniazid in addition to isoniazid itself and acetylisoniazid in the plasma of patients. In initial pharmacokinetic applications of the method, it has been shown that plasma INHG-Na is a stable substance that liberates only negligible concentrations of INH.

In a pilot study involving 62 patients with open pulmonary tuberculosis, we established that slow acetyators and patients receiving intravenous rifampicin treatment showed a tendency towards a more rapid negativisation of the sputum culture than did fast acetyators (lower levels of isoniazid) or patients receiving oral rifampicin therapy (decreasing bioavailability of the rifampicin during treatment).

We investigated the pharmacokinetic interaction of RMP (administered from the first day of treatment onwards), PZA (given from the second day onwards), and INH (day 17 onwards) in ten, previously untreated patients with pulmonary tuberculosis (five slow acetylators and five fast acetylators). In the case of the slow acetylators, higher INH and acetylhydrazine concentrations were measured than in the fast acetylators. RMP revealed the well-known autoinduction of its metabolism. During the course of continuing treatment, the PZA levels increased. No increased incidence of hepatoxic reactions was to be seen.