Trial reportBritish journal of clinical pharmacology1998
The influence of drug input rate on the development of tolerance to frusemide.
Trial report in British journal of clinical pharmacology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed, 14 citations in OpenAlex.
- Understanding the hysteresis loop conundrum in pharmacokinetic/pharmacodynamic relationships.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2014Article
- The efficiency concept in pharmacodynamics.Clinical pharmacokinetics · 1999Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsUnderstanding the impact of drug input rate on its pharmacokinetic-pharmacodynamic relationship may lead to a more optimal drug therapy. The aim of the present study was to investigate the influence of the rate of administration on tolerance development to frusemide, by giving the drug at four different infusion rates.
methodsEight healthy volunteers were given 10 mg of frusemide on four different occasions, as a constant-rate intravenous infusion during 10, 30, 100 and 300 min, respectively. Urinary volume and contents of frusemide and sodium were measured in samples collected over 8 h.
resultsThe four different infusion rates systematically influenced the frusemide excretion rate versus diuretic and natriuretic response relationship. Counter-clockwise hysteresis occurred for the most rapid infusion rate, whereas a progressive clockwise hysteresis was observed for the slower infusions, indicating development of tolerance. For each subject, diuresis and natriuresis were modeled for all four treatments simultaneously, using a feedback tolerance model. It was not possible to describe the data using a model without tolerance. The time course of tolerance development showed remarkable differences between the infusion rates. The intensity of maximum tolerance development was significantly less for the slowest infusion rate compared with the more rapid infusions and it appeared significantly later. However, no differences in diuretic or natriuretic response were found between the treatments.
conclusionsThe direction of the hysteresis loop is dependent on the input rate of frusemide. After the administration of a single low dose of frusemide, the time course of tolerance, rather than the integrated time course of tolerance, is influenced by the drug input rate.
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