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Clinical pharmacokinetics of intramuscular thiazinamium methyl sulfate.

The disposition of the quaternary ammonium compound thiazinamium methyl sulfate is described after intramuscular injection in humans. The plasma concentration-time curves could be resolved into two exponential components, suggesting an open two-compartment model with absorption phase. Absorption was found to be extremely fast. Peak concentrations were always reached within 20 min, but in the majority of cases they were found to be between 6 and 10 min. Occasionally, the first sample (t = 3 min) proved to contain the highest concentration. Apparently the high solubility of the drug in the interstitial fluid is of prime importance for rapid absorption. Injection technique and the injection site seemed to be important for the final profile of the plasma concentration-time curve. Distribution was found to be very fast as well, with a half-life of approximately 20 min, and the apparent volume of distribution for the central compartment was about 40-60 l. Muscle activity and hence increased capillary blood flow during the distribution phase may result in a second peak in the plasma concentration-time curve. The distribution phase is followed by an elimination phase with a much longer half-life (mean value 375 min) and a volume of distribution of approximately 200-400 l. The total body clearance for thiazinamium methyl sulfate was found to be high (mean value about 800 ml/min), suggesting an active excretion process.