[Erythrocyte/plasma ratio of lithium. Determination method and individual stability].
Lithium is a very efficient drug for the treatment of maniac-depressive psychosis, but its therapeutic index is narrow. Moreover, even with lithium plasmatic concentrations in the therapeutic range, some patients showed toxic signs when others seemed not to be efficiently treated. The measurement of erythrocyte lithium concentration might provide a more rational method than the measurement of plasma lithium for monitoring the course of lithium therapy, since the mechanisms of lithium transfer across red blood cells resemble those for neurons. Toxic effects could then be related to high lithium erythrocyte concentrations or a high erythrocyte/plasma lithium ratio (EPR). The intracellular lithium concentration depends mainly on the Li(+)-Na+ countertransport, which is genetically determined. We wondered therefore whether the EPR is a specific characteristic of each patient and how long it requires to stabilise when lithium therapy is started. The EPR was determined by directly measuring the plasma and erythrocyte concentrations with a carefully standardised assay (lithium carbonate administered at 7 pm, blood sample taken at 7 am the next day). Potassium edetate was preferred as anticoagulant to sodium heparinate, which gave an overestimation of EPR. Plasma trapped in the red cell column, with polyfructosan as marker, was found to average 4% in our assay conditions (centrifugation at 3,200 g, 15 min, 4 degrees C). This standardised assay makes it possible to determine the EPR very accurately with an inter-assay variation coefficient of about 2.4%. Following the start of lithium therapy, the EPR stabilised very quickly, mainly within two days (three out of four patients), at a time when lithium erythrocyte and plasma concentrations were still increasing.(ABSTRACT TRUNCATED AT 250 WORDS)
Barthelmebs
M
M
Institut de Pharmacologie, URA D0589 CNRS, Université Louis Pasteur, Strasbourg.
Ehrhardt
J D
JD
Schweitzer-Ehret
A
A
Danion
J M
JM
Imbs
J L
JL
D000328:Adult; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy / Q000523:psychology; D003866:Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006760:Hospitalization; D006801:Humans; D016651:Lithium Carbonate / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D016651:Lithium Carbonate
Le rapport érythroplasmatique du lithium. Méthode de mesure et stabilité individuelle.