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Pharmacokinetics of a single oral dose of hydroflumethiazide in health and in cardiac failure

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Summary

The pharmacokinetics of hydroflumethiazide (HFT) were investigated after single oral doses of 6 µmoles/ per kg body weight in five healthy subjects and in nine patients with moderate cardiac failure. HFT was excreted in urine together with 2,4-disulfamyl-5-trifluoromethylaniline (DTA), which was also present in the blood after administration of HFT. HFT and DTA were determined by TLC and spectrofluorodensitometry. Mean cumulative urinary excretion of HFT was 46.5 and 47.5 per cent of the dose both in healthy subjects and in patients. Distribution half-life (t1/2α) was about 2 h in both groups of subjects, while biological half-life (t1/2β) ranged from 12.4 to 26.9 h (mean 16.6) in healthy subjects, and from 6.3 to 13.7 h (mean 9.6) in patients. Mean renal clearance was 0.33 and 0.211 · h−1 · kg−1 in normal subjects and patients, respectively, and was almost equal to the total body clearance. HFT had a large apparent volume of distribution (Vβ), with mean values of 6.4 and 3.11 · kg−1 in normal subjects and patients. Mean cumulative urinary excretion of DTA was 1.8 and 1.9 per cent in healthy subjects and patients with cardiac failure. The apparent half-life of DTA, determined from urinary excretion rate in eleven subjects, ranged from 16 to 56 h but half-lives in three others were more than 100 h. The results indicate that HFT is partly metabolized in the body to DTA, and DTA and HFT are excreted in urine. The half-life of DTA was longer than that of the parent drug. The apparent volume of distribution, clearance and biological half-life of HFT were lower in patients with cardiac failure than in healthy subjects.

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Authors and Affiliations

  1. Institute of Pharmacology, University of Oslo, Oslo, Norway

    O. Brørs & S. Jacobsen

  2. Medical Department VII, Ullevål Hospital, Oslo, Norway

    E. Arnesen

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  1. O. Brørs
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  2. S. Jacobsen
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  3. E. Arnesen
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Brørs, O., Jacobsen, S. & Arnesen, E. Pharmacokinetics of a single oral dose of hydroflumethiazide in health and in cardiac failure. Eur J Clin Pharmacol 14, 29–37 (1978). https://doi.org/10.1007/BF00560255

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  • DOI: https://doi.org/10.1007/BF00560255

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