Lithium Pharmacokinetics, Duration of Therapy, and the Adenylate Cyclase System

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Abstract
The elimination half-life of Li2CO3 in red blood cells, plasma and urine was measured in 30 patients hospitalized for primary affective disorders. The duration of Li treatment at the time of sampling had a direct effect on lengthening time-course. Those on their initial course of Li had the lowest half-lives (in days): 1.12 (urine), 1.28 (plasma) and 1.22 (red blood cells); those with < 1 yr of Li had intermediate values: 1.85, 1.65 and 1.75, and those with > 1 yr of continuous Li administration had the highest mean half-lives: 2.40, 2.43 and 2.24. The significance of these results for urine (P < 0.01) and plasma (P < 0.05) indicated that Li may stimulate the production of an endogenous regulator of Li efflux. Of these patients, 8 had lumbar punctures before Li administration: those with previous treatment with Li had higher mean cAMP levels than those taking it for the 1st time. These results are discussed in the context of the possible mechanisms of Li action.