Trial reportBritish journal of clinical pharmacology1998
The time of maximum effect for model selection in pharmacokinetic-pharmacodynamic analysis applied 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 9 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.
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Who cites it
9 citing papers in PubMed.
- Indirect-response modeling of desmopressin at different levels of hydration.Journal of pharmacokinetics and biopharmaceutics · 1999Trial
- The influence of frusemide formulation on diuretic effect and efficiency.British journal of clinical pharmacology · 1999Trial
- The influence of drug input rate on the development of tolerance to frusemide.British journal of clinical pharmacology · 1998Trial
- A tutorial for model-based evaluation and translation of cardiovascular safety in preclinical trials.CPT: pharmacometrics & systems pharmacology · 2024Article
- Modelling the delay between pharmacokinetics and EEG effects of morphine in rats: binding kinetic versus effect compartment models.Journal of pharmacokinetics and pharmacodynamics · 2018Article
- A dynamical systems analysis of the indirect response model with special emphasis on time to peak response.Journal of pharmacokinetics and pharmacodynamics · 2005Article
- Pharmacokinetic-pharmacodynamic modeling of the electroencephalogram effect of imipenem in healthy rats.Antimicrobial agents and chemotherapy · 2001Article
- Modeling of pharmacokinetic/pharmacodynamic (PK/PD) relationships: concepts and perspectives.Pharmaceutical research · 1999Article
- Methodological issues in pharmacokinetic-pharmacodynamic modelling.Clinical pharmacokinetics · 1998Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsBoth indirect-response models and effect-compartment models are used to describe the pharmacodynamics of drugs when there is a delay in the time course of the pharmacological effect in relation to the concentration of the drug. The aim of this study was to investigate whether the time of maximum response after single-dose administration at different dose levels could be used to distinguish between these models and to select the most appropriate pharmacokinetic-pharmacodynamic model for frusemide.
methodsThree doses of frusemide, 10, 25 and 40 mg were given as rapid intravenous infusions to five healthy volunteers. Urine samples were collected for 5 h after dosing. Volume and sodium losses were isovolumetrically replaced with an intravenous rehydration fluid. Diuresis and natriuresis were modelled for all three doses simultaneously, applying both an indirect-response model and an effect-compartment model with the frusemide excretion rate as the pharmacokinetic input.
resultsThe observed time of maximum diuretic and natriuretic response significantly increased with dose. This increase was well predicted by the indirect-response model, whereas the modelling with the effect-compartment model led to a poor prediction of the peaks. There was no difference between the observed and predicted time of maximum diuretic and natriuretic response using the indirect-response model, whereas the time of maximum response predicted by the effect-compartment model was significantly earlier than the time observed for the 25 mg (P < 0.05) and 40 mg (P < 0.05) doses.
conclusionsThe time of maximum response to frusemide was better described using an indirect-response model than an effect-compartment model. Studying the time of maximum response after administration of different single doses of a drug may be used as a selective tool during pharmacokinetic-pharmacodynamic modelling.
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