The relationship of the lithium erythrocyte: plasma ratio to plasma lithium level.

The relationship of the lithium erythrocyte:plasma ratio to plasma lithium concentration was reviewed in inpatients and outpatients with affective disorders. For some patients, there was a linear correlation between the erythrocyte lithium:plasma lithium ratio and the plasma lithium concentration. For these patients a graph of the slopes and intercepts of the lithium erythrocyte:plasma ratio vs. plasma lithium data formed a line that was not significantly different from the data of Lee et al. (1975). Significant correlations were found between the slopes and intercepts of the lithium erythrocyte:plasma ratio vs. plasma lithium data and the magnitude of active lithium efflux (Ko) from the erythrocyte. Our data confirm the finding of Lee et al. (1975) that the lithium erythrocyte:plasma ratio is dependent on the plasma lithium concentration. We relate this finding to lithium efflux from the erythrocyte.     

The effect of enalapril on serum lithium levels in healthy men.

BACKGROUND: Several authors have recently described the development of lithium toxicity after the addition of angiotensin-converting enzyme inhibitors to a stable lithium regimen. This pilot study was designed to systematically investigate the effects of enalapril, an angiotensin-converting enzyme inhibitor, on the serum level of lithium. METHOD: In a 26-day outpatient study, nine healthy men took lithium for 10 days, lithium and enalapril for 10 days, and lithium alone again for 6 days. Serum lithium levels were measured while patients were taking lithium alone and while they were taking the lithium/enalapril combination. RESULTS: There were no statistically significant differences between mean serum lithium level during treatment with lithium alone and during treatment with the lithium/enalapril combination. However, one subject showed a 31% increase in serum lithium level after enalapril was added. CONCLUSION: Although no statistically significant differences between mean serum lithium level during treatment either with lithium alone or with lithium/enalapril were found, it is possible that the low dose of enalapril and low serum lithium levels employed for subject safety may have resulted in a type II statistical error. If enalapril doses or initial serum lithium levels were similar to those described in case reports, a significant difference in mean serum lithium levels may have been observed. While a predictable interaction between lithium and enalapril probably does not occur in all patients, factors such as enalapril dose, serum lithium level before addition of enalapril, or the presence of heart disease may make such an interaction more likely. At the levels of lithium and enalapril used in this study, elevated serum lithium concentration does not appear to be a universal event, but physicians must exercise appropriate caution.     

Relationship between plasma, RBC, and CSF lithium concentrations in human subjects

Simultaneous measurement of plasma, RBC, and plasma lithium concentrations took place with 17 inpatients chronically treated with lithium, at various times after the last lithium dose. RBC lithium levels were significantly higher than CSF lithium levels. Specimens drawn 10 or more hours after the last dose showed higher RBC and CSF lithium and lower plasma lithium than specimens drawn 4 or less hours after the last lithium dose. None of the lithium measurements differentiated manic-depressives from schizophrenics or schizoaffectives. Plasma, RBC, and CSF lithium all intercorrelated highly and equally.     

Lithium toxicity: when is hemodialysis necessary?

A case of severe lithium intoxication is presented in which the function of the lithium pump was monitored, and was found to improve as the signs of lithium toxicity abated. The status of the lithium pump may provide an index of the severity of lithium intoxication. Since the lithium pump regulates the extrusion of lithium from the intracellular to the extracellular space, it is argued that the activity of the lithium pump is an index of the severity of lithium intoxication and crucial to the process of detoxification.     

临床医师应用血锂测定情况调查分析

目的调查临床医师实际应用血锂测定情况。方法自制调查表，内容包括年龄、性别、诊断、病程、测量血锂次数、测量血锂时的碳酸锂剂量、测量血锂时应用锂盐治疗的时间、测量血锂的原因、血锂测量结果、测量血锂前后的血白细胞数，应用SPSS软件包对数据进行统计分析。结果每位患者血锂测量最少1次，最多6次。测量血锂的医嘱绝大多数为常规检查。绝大多数病例血锂浓度值在正常范围内，极少数病例超出正常值。随着治疗时间的延长，测量血锂的意义下降。结论血锂测量绝大多数为常规检查，随治疗时间的延长，测量血锂次数和人数逐渐减少，测量血锂的意义也下降。但愿结合临床观察，随时检查血锂浓度，以防和早期发现锂盐中毒。     

Serum lithium minimum and diuresis

Serum lithium was analyzed over a 24-hour period in patients who were receiving lithium in one daily dose. Linear regression was performed with urine volume as the independent variable and lithium dose, maximum serum lithium concentration. 12-hour serum lithium, minimum serum lithium, length of treatment, and age of patients as the dependent variables. Only minimum serum lithium and urine volume showed a good positive correlation.     

Lithium and neuroleptic drugs in combination - effect on lithium RBC/plasma ratio

The lithium RBC/plasma ratio was determined in 59 patients during prophylactic lithium therapy. No relationship was found between the lithium RBC/plasma ratio and sex, age, type of illness, weight, lithium dosage, duration of treatment or lithium plasma level. However, patients taking a combination of lithium and neuroleptic drugs had significantly higher lithium RBC/plasma ratios than patients taking lithium without neuroleptic drugs. The results are in line with earlier in vitro studies and are discussed in relation to the high frequency of neurotoxic and nephrotoxic adverse effects noted in patients taking a combination of lithium and neuroleptic drugs.     

Ibuprofen can increase serum lithium level in lithium-treated patients

The interaction between lithium and ibuprofen was studied in nine male patients admitted to the geropsychiatric ward of a veterans administration medical center. The patients, diagnosed as having bipolar affective disorder or schizoaffective disorder, who had been kept on a steady-state lithium level, received lithium for 3 days, then lithium and ibuprofen (1800 mg/day) for 6 days, and then lithium for 5 days. Ibuprofen increased the serum lithium level and decreased the lithium clearance with marked interindividual variations. These findings indicate that lithium dosage may need to be reduced in some patients following initiation of ibuprofen therapy. There was no significant correlation between changes in lithium serum level and creatinine clearance. The possibility that a tubular renal prostaglandin system may affect lithium excretion needs further investigation.     

Lithium distribution in mania: plasma and red blood cell lithium, clinical state, and monoamine metabolites during lithium treatment

We examined red blood cell (RBC) and plasma lithium concentrations and RBC/plasma lithium ratios in 14 manic patients during lithium treatment as part of the National Institute of Mental Health's Collaborative Program on the Psychobiology of Depression, Biological Studies. All of the lithium measures increased during treatment, especially RBC lithium. There were positive correlations between the RBC lithium concentration and the RBC/plasma lithium ratio and their maximal values in a single-dose pharmacokinetic experiment before treatment. After 5 and 16 days of treatment, patients with good subsequent outcome had higher RBC/plasma lithium ratios than did patients with poor outcome. Early in treatment, there was a negative correlation between lithium concentrations and severity of mania. During treatment, there was a negative correlation between RBC lithium and urinary MHPG excretion. There was a positive correlation between RBC or plasma lithium during the first few days of treatment and subsequent reduction in norepinephrine excretion during treatment. At 3 weeks, there were negative correlations between reductions in catecholamine measures and lithium concentrations. These data suggest that there are changes in the sensitivity of behavior and catecholamine function to lithium during treatment. RBC concentrations of lithium appear to be a potentially useful indicator of its behavioral and neurochemical effects.     

Failure of sulindac to increase serum lithium levels

The interaction of sulindac with lithium was investigated in four patients who were admitted to a geropsychiatry ward and required lithium therapy. Sulindac 300 mg/day failed to affect lithium serum level and renal lithium clearance in these patients. Sulindac seems safer in patients receiving lithium than drugs like indomethacin, which can substantially increase serum lithium levels.     

Interdependency of lithium ratio, plasma lithium level and clinical state in patients with affective disorders

The interrelationship between lithium ratio, lithium plasma level and the different clinical phases of 31 patients with bipolar affective disorder has been investigated. the interdependency of these variables was followed longitudinally during different phases of the illness while under lithium therapy. Although positive correlations between lithium ratio and lithium plasma levels were evident, the lithium ratio values in the euthymic group were significantly higher than those in the manic and depressive groups, independently of the plasma lithium level. Our data suggested that RBC/plasma lithium ratio might be a sensitive state dependent index in affective bipolar illness.     

Comparison between saliva and serum lithium concentrations in patients treated with lithium carbonate.

The relation between serum and saliva lithium concentration was studied in patients treated with lithium carbonate. In 23 patients a highly variable saliva/serum ratio was found in simultaneous saliva and serum samples. In five patients studied during a period of 4-8 weeks three patients showed a high fluctuation in saliva/serum lithium ratio. In 20 patients saliva lithium concentrations varied unexpectedly in a second sample produced after 15 min. Although some authors report a high and stable relation between saliva and serum lithium concentration, we consider the saliva lithium level unreliable as a prediction of the serum lithium level in patients treated with lithium carbonate.     

Correction of lithium levels for dose and blood sampling times

Inconsistencies inherent in the clinical application of morning serum lithium levels can be eliminated by correcting the levels for variations in dosage schedule, rate of lithium elimination, and blood sampling time. In this report, graphs constructed from an accurate pharmacokinetic model of lithium elimination are used to convert the serum lithium level into the daily exposure of the body to lithium. This method facilitates safety and effectiveness in lithium treatment and enables outpatient blood samples for lithium levels to be conveniently drawn in the afternoon.     

Studies on the use of blood lithium concentrations in lithium therapy in Japan

The relationship between the concentration of lithium in whole blood and plasma was determined in 11 manic-depressive patients 12 h after the evening dose of lithium carbonate taken in the form of slow release tablets (Limas). Significant relationships were found between the concentration of lithium in whole blood and plasma as well as between the daily dose of lithium and the lithium concentration in whole blood and in plasma. The findings suggest that under certain conditions the concentration of lithium in a small sample of whole blood may be used to monitor lithium therapy in outpatients. The advantages of using whole blood are discussed.     

Lithium prevents adaptation of brain dopamine systems to haloperidol in schizophrenic patients

To evaluate the effect of lithium treatment on haloperidol-induced changes of brain dopamine systems, cerebrospinal fluid homovanillic acid (HVA) was assessed in nine patients during a sequential treatment protocol with placebo, lithium, lithium plus acute haloperidol, and lithium plus chronic haloperidol. None of the patients developed tolerance to the rise in HVA during treatment with haloperidol and lithium. Concurrent treatment with lithium appears to prevent the development of tolerance in dopamine metabolism during chronic haloperidol treatment. These data provide the first evidence in man that lithium may prevent neuroleptic-induced functional supersensitivity of brain dopamine systems.     

Lithium incorporation in the fibroblasts of manic-depressives

Lithium incorporation in cultured human skin fibroblasts was measured in a group of 10 manic-depressives and 10 controls. This system was believed to eliminate many of the sources of variability to which measurement of the lithium ratio in erythrocytes (RBCs) is subject. A fibroblast lithium ratio calculated from 1-hr lithium incorporation studies correlated highly with an in vitro RBC lithium ratio in medication-free controls. Manic-depressives and controls did not differ in lithium incorporation or fibroblast lithium ratio, leading to the conclusion that the lithium ratio is probably not a good measure for differentiating the two populations.     

Theophylline precipitated alterations of lithium clearance

ABSTRACT– The effect of steady state therapeutic theophylline serum levels on lithium clearance was investigated. A significant increase in lithium clearance occurred with the administration of theophylline. Despite considerable intersubject variability, a direct lithium clearance estimation method demonstrated a mean increase of 30% with the addition of theophylline. The concomitant use of lithium and theophylline potentially may alter lithium levels sufficiently to result in manic or depressive relapses in patients receiving lithium prophylactically.     

Effect of abrupt change from standard to low serum levels of lithium: a reanalysis of double-blind lithium maintenance data

OBJECTIVE: Growing evidence suggests that abrupt lithium discontinuation increases the risk of recurrence for patients with bipolar disorder. To assess the effect of abrupt change in lithium dose, the authors reanalyzed data from a previously reported, randomized, double-blind trial of standard- versus low-dose lithium for maintenance therapy in bipolar disorder. METHOD: In the original study, serum lithium levels were obtained during a 2-month open stabilization period for 94 patients with bipolar disorder who were then randomly assigned to be maintained on a low (serum level=0.4-0.6 meq/liter) or a standard (0.8-1.0 meq/liter) level of lithium therapy. Patients were then followed for up to 182 weeks. This reanalysis examined the potential confounding influence of prerandomization lithium level and change in lithium level on the outcome of subjects assigned to a standard or low maintenance dose of lithium. RESULTS: In a Cox proportional hazards model incorporating pre- and postrandomization lithium levels and the interaction of these factors, only the interaction term remained significantly associated with time to recurrence. CONCLUSIONS: The findings indicate that change in serum lithium level may be a more powerful predictor of recurrence of bipolar disorder than the absolute assignment to a low or a standard dose of lithium and suggest that an abrupt decrease in lithium level should be avoided. This reanalysis did not directly address optimal maintenance lithium levels but raises questions about the original study's finding of superiority for lithium levels > or =0.8 meq/liter. The results underscore the importance of accounting for the possible confounding effects of changes in the intensity of pharmacotherapy in studies of maintenance therapies for bipolar disorder.     

Effects of GTP on hormone-stimulated adenylate cyclase activity in cerebral cortex, striatum, and hippocampus from rats treated chronically with lithium

The effects of lithium on guanosine triphosphate (GTP) stimulated adenylate cyclase activity and hormone-induced GTP activation of the enzyme have been studied in three regions of the rat brain. Chronic treatment with lithium, giving a serum lithium level of 0.71 +/- 24 mmol/L, reduced isoprenaline-induced GTP stimulation of adenylate cyclase activity in cortical membranes at concentrations of GTP up to 2 microM. No effect of lithium was observed at higher concentrations of GTP. The enzyme activity stimulated by GTP alone was unaltered by lithium ex vivo. In striatal membranes, lithium ex vivo decreased both dopamine-induced GTP activation of adenylate cyclase and GTP-stimulated adenylate cyclase activity at concentrations of GTP below 2 microM. No effects of lithium ex vivo were found in striatum at 2 microM GTP and above. In hippocampal membranes, lithium ex vivo did not influence either serotonin-induced GTP stimulation of the adenylate cyclase or GTP-stimulated enzyme activity at low levels of GTP. However, at 50 microM GTP, lithium ex vivo enhanced serotonin-stimulated enzyme activity. The present results suggest that lithium ex vivo decreases neurotransmitter activation of the cortical beta-adrenergic adenylate cyclase by influencing the mechanisms by which receptor agonists enhance the GTP stimulation of the adenylate cyclase. Furthermore, lithium ex vivo exerts a region-specific action on the brain adenylate cyclases, but in the brain regions studied, an effect of lithium on N-protein level might be of significance for the action of lithium ex vivo on neurotransmitter activation.     

Implication of serum concentration monitoring in patients with lithium intoxication

The aim of the present study was to determine the relationships between serum lithium level, duration of lithium intoxication, severity of symptoms, and the outcome of the disease. Subjects with a serum lithium level of >/=1.2 mEq/L were included in the study. Seventy-eight patients with lithium intoxication were identified between 1 July 1999 and 31 December 2002. The demographic characteristics, clinical manifestations, and concomitant medications were recorded. Most patients with acute lithium intoxication had mild symptoms, independent of the serum lithium levels. In patients with chronic lithium intoxication, the frequency of severe symptoms was higher than in those with acute intoxication. None of the 78 intoxicated patients in the present survey died or suffered from persistent neurological sequelae. Patients with concomitant medications, older age, and existing neurological illness may have an increased susceptibility to lithium toxicity. Regular monitoring of serum lithium level is essential for lithium-treated patients. Clinicians should pay attention to patients with pre-existing neurological illness, older age, or receiving medications that may interact with lithium.