Er «Det Terapeutiske Interval» og 12h-stSLi i realiteten valide ved dosering på basis af koncentrationsmonitorering? Vurdering bl.a. ved hjælp af en farmakokinetisk simulationsmodel

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Abstract
Does any validity exist of a «therapeutic interval» and 12h-stSLi in dosing based on monitoring of 12h serum lithium? Any one of the stated «therapeutic intervals» for serum lithium (SLi) is arbitrary and without substantial documentation. A claim of a «close relationship» between 12h-SLi and renal distal water reabsorption (V/CLi) is undoubtedly incorrect. The biological half-life (t1/2) of SLi has a right-skewed distribution from ab. 10 to ab. 50 hours. This alone would demand a «therapeutic window» of 0.40.-1.10 mmol/l for 12h-stSLi. The other pharmacokinetic parameters with biological variation would demand further width. Formulatory uncertainties of the lithium preparation are involved too. In addition the demand of width of the «window» is enhanced by the intraindividual insecurity of 12h-SLi and that of the chemical analysis. Establishment of a narrow «therapeutic interval» for 12h-SLi is an illusion. Probably the consequences of the previous use of «therapeutic intervals» have been that many patients have received an insufficient lithium dosage and a few have been pushed into iatrogenic intoxications. 12h-stSLi is indispensable in treatment control of the individual patient, provided consummate compliance of the patient concerning dose regimen and timepoint of blood-drawing in relation to the last dose in the evening. 12h-stSLi >1.40 mmol/l should still be considered a bad omen indicating risk of intoxication.

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