Lack of effect of amisulpride on the pharmacokinetics and safety of lithium

Abstract

Lithium may be used as adjuvant therapy in schizophrenic patients and antipsychotics can be employed during the early phases of lithium therapy in patients with bipolar disorder. The issue of interactions between lithium and antipsychotics is therefore important. This study investigates the potential influence of repeated administration of amisulpride, an atypical antipsychotic, on the pharmacokinetics of lithium at steady state. Twenty-four healthy male volunteers (aged 1833 yr) received lithium carbonate (500 mg b.i.d.) for 14 d. All subjects were shown to have stable lithium serum concentrations after 57 d and were then randomized to receive double-blind administration of amisulpride (100 mg b.i.d.) or placebo bid from day 8 of lithium administration. Complete pharmacokinetic profiles were obtained on days 7 and 14 for lithium and trough plasma concentrations on days 10, 12 and 14 for amisulpride. Co-administration of amisulpride appeared to exert no effect on the pharmacokinetics of lithium. All treatments were well tolerated and safety assessment revealed no differences between the lithium+placebo and lithium+amisulpride groups. This finding permits the flexible use of amisulpride in patients already receiving lithium therapy.

Amisulpride doses and plasma levels in different age groups of patients with schizophrenia or schizoaffective disorder

“…In the present study, lithium co-medication was reported in only 2.5% of patients and showedin some contrast to the results of Bergemann, et al (2004) no substantial influence on dose-corrected ASU plasma levels. Several other factors, which could have influenced the renal elimination of ASU (Canal, et al, 2003;Bergemann, et al, 2004;, had, however, not been excluded in the present study.…”

“…Moreover, ASU shows only a low plasma protein binding affinity (16%), almost no interaction with hepatic cytochrome P450 dependent enzymes, and is renally eliminated to a very great extent without metabolites (Caccia, 2000;2002). Dose-adjustment has to take place in patients with renal insufficiency (Caccia, 2000); however, potential interactions with other renally eliminated substances (e.g., lithium) have not been reported unequivocally (Canal, et al, 2003;Bergemann, et al, 2004). In healthy elderly volunteers aged 65-79, a single oral dose of ASU 50 mg showed a pharmacokinetic profile similar to that of young subjects (Hamon-Vilcot, et al, 1998).…”

Population Pharmacokinetics of Lithium in Young Pediatric Patients With Intellectual Disability

“…Moreover, the current lithium dose regimen is mainly for bipolar disorder therapy, which generally needs high serum concentrations and therefore has a narrow therapeutic window of 0.6-1.2 mmol/L and a maintenance therapy window of 0.6-0.8 mmol/L (Methaneethorn and Sringam, 2019). The PK properties of lithium treatment in adults have been reported previously (Wing et al, 1997;Canal et al, 2003;Wong et al, 2011), but studies on the PKs of lithium in young pediatric patients are rare. One PK study in nine children aged 10-12 years and diagnosed with behavioral disorder or adjustment disorder receiving a single dose of 300 mg lithium carbonate suggested that the PK parameters were similar to those of adults, except for the higher total clearance in children (Vitiello et al, 1988).…”

Antioxidant and electrochemical properties of calcium and lithium ascorbates

“…Lithium influences on neurochemical processes proceeding in a brain [3]. It is established, that lithium ions are able to stop acute maniac excitation, and it may be used as adjuvant therapy in schizophrenic patients [4][5][6]. Lithium is still the first drug of choice for treatment of affective disorders [7,8].…”