Relationship between standardized twelve-hour serum lithium, mean serum lithium of the 24-hour day, dose regimen, and therapeutic interval. An evaluation based on pharmacokinetic simulations.
In conclusion, it may be stated that the twelve-hour serum lithium value is essentially arbitrary and can only be used as an unambiguous guide in an intraindividual context. A single SLi value which correlates strongly enough with any of the known clinical responses to lithium to be of clinical importance is as yet unknown, with the one exception that impending lithium intoxication must be regarded as so serious a condition that the interindividually ambiguous 12h-stSLi should generally be regarded as a bad omen when it reaches levels above 1.40 mmol/l. Given that the working hypothesis (that the 24-hour mean of SLi is of crucial importance for many of the clinical effects of long-term lithium treatment) is correct, and in view of interindividual variations in human lithium pharmacokinetics, it cannot be generally acceptable to lower and narrow the "therapeutic range" to, for example, 0.50-0.80 mmol/l. Correspondingly, the suggestion that the daily dose should be kept below arbitrarily chosen low lithium dosages is irrelevant; it is clear that 12h-stSLi and the daily dose should be individualized within wider parameters, with due consideration of the biological half-life of lithium in the particular patient, the desired MSLi, and the absorption rate of lithium, which mainly depends on the dissolution properties of the drug preparation. In general, no strong correlation between the 12h-stSLi and the mean SLi over the 24-hour day can be expected as far as representative groups of lithium patients are concerned.
D002940:Circadian Rhythm; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008094:Lithium / Q000008:administration & dosage / Q000097:blood*; D008954:Models, Biological
D008094:Lithium