ArticleClinical pharmacokinetics2000
A concept for pharmacokinetic-pharmacodynamic dosage adjustment in renal impairment: the case of aminoglycosides.
Article in Clinical pharmacokinetics, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 4 papers.
What it found
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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.
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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
4 citing papers in PubMed, 8 citations in OpenAlex.
- Aminoglycosides in septic shock: an overview, with specific consideration given to their nephrotoxic risk.Drug safety · 2013Review
- Mechanism-based pharmacokinetic-pharmacodynamic modeling of antimicrobial drug effects.Journal of pharmacokinetics and pharmacodynamics · 2007Review
- Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids.Clinical pharmacokinetics · 2005Review
- Comparison of gentamicin dose estimates derived from manual calculations, the Australian 'Therapeutic Guidelines: Antibiotic' nomogram and the SeBA-GEN and DoseCalc software programs.British journal of clinical pharmacology · 2004Article
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFor patients with impaired renal function, dosage adjustment is necessary for many drugs. Adjustment with respect only to pharmacokinetic parameters may be insufficient.
objectiveTo apply the theory of pharmacokinetics and pharmacodynamics to derive a mathematical model that links the concentration-time course and the clinical response by means of the pharmacokinetic-pharmacodynamic parameter 'area under the effect-time curve' (AUETC), and to use this analysis and clinical data for aminoglycosides to calculate dosage adjustments in renal impairment.
methodsModel parameters were estimated for the antimicrobial and nephrotoxic effects of aminoglycosides on the basis of data from the literature. Effect parameters were calculated for various degrees of impaired renal function.
resultsUse of the model parameters gave a high correlation between the predicted and the observed (literature) values for antimicrobial efficacy and nephrotoxicity. When calculating dosage adjustments in renal impairment, it was possible to hold only one effect (antimicrobial or nephrotoxic) constant by dosage adjustment, whereas the other changed unfavourably. This was explained by differences between the pharmacodynamic parameters for each effect. For high antimicrobial efficacy, a target peak concentration of 9 mg/L (for gentamicin) should be obtained every 48 hours in advanced renal impairment. For low nephrotoxicity, the peak concentration should not exceed 3 mg/L.
conclusionsThe parameter AUETC could be a useful pharmacokinetic-pharmacodynamic surrogate marker for dosage adjustment in renal impairment. Using the AUETC method, the beneficial effect can be balanced against the adverse effect.
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