Lithium Carbonate Tablets Research Articles

Plus ça change? Switching lithium preparations.

A supply disruption alert in 2020, now rescinded, notified UK prescribers of the planned discontinuation of Priadel® (lithium carbonate) tablets. This service evaluation explored lithium dose and plasma levels before and after the switching of lithium brands, in order to determine the interchangeability of different brands of lithium from a pharmacokinetic perspective. Data on the treatment of 37 patients switched from Priadel® tablets were analysed. Switching to Camcolit® controlled-release tablets at the same dose did not result in meaningful differences in plasma lithium levels. Dose adjustment and known or suspected poor medication adherence were associated with greater variability in plasma lithium levels on switching brands. For comparable pre- and post-switch doses in adherent patients, the most common brands of lithium carbonate appear to produce similar plasma lithium levels. British National Formulary guidance relating to switching lithium brands may be unnecessarily complex.

P1113TREATMENT OF ACUTE LITHIUM INTOXICATION WITH SUSTAINED LOW-EFFICIENCY DIALYSIS (SLED)

Abstract Background and Aims Lithium salts are widely used in psychiatry for prophylaxis and treatment of bipolar affective disorders. Given its narrow therapeutic range, drug overdosage is not infrequent, and lithium intoxication has potentially fatal neurologic and cardiac side effects. Owing to its low molecular weight (7 Da), relatively small volume of distribution, and its negligible protein binding, lithium can be efficiently removed by any extracorporeal modality of renal replacement therapy (RRT). Although conventional intermittent haemodialysis (IHD) is effective in promptly cleating lithium, postdialysis rebound is common. The use of sustained low-efficiency dialysis (SLED) in lithium intoxication seems to be a valid therapeutic strategy, but strong evidence is still lacking in the literature. We present here two cases of lithium intoxication, in one case acute (naïve patient) and in the other case acute-on-chronic (a deliberate overdose in a patient previously on lithium therapy), successfully treated with SLED. Method: Patient A - A 47 years-old woman without history of lithium consumption was admitted to the ER. after a voluntary acute lithium ingestion of 40 tablets of lithium carbonate (8.12 mEq lithium each). Notwithstanding treatment with intravenous crystalloids and gastric lavage, lithium concentration increased up to 4.18 mEq/l at about 24 h after admission. She developed mental status changes, oliguria, hypotension and bradycardia. Patient B – A 58 years-old man on lithium therapy for bipolar syndrome was admitted to ER after a voluntary acute lithium ingestion of an unknown quantity of lithium carbonate tablets. Lithium concentration, after an initial level of 0.4 mEq/L, increased up to 4.35 mEq/l about 15 h from admission, despite irst-line therapies with intravenous crystalloids and gastric lavage were promptly started. His mental status worsened, together with oliguria, bradycardia and hypotension. Results: Patient A - A 8-hour SLED session with regional citrate anticoagulation (RCA) was planned [blood flow rate (Qb) 200 mL/min; dialysis fluid rate (Qd) 300 mL/min; countercurrent flow direction]. Lithium serum levels decreased by 87% during treatment (0.55 mEq/L), and the patient fully awoke recovering a normal mental status within the first 4 h of treatment. SLED was completed safely within the prescribed time. After the end of treatment, lithium rebound was unremarkable and renal function completely recovered and the patients was discharged after 3 days. Patient B - A 12-hour SLED session with RCA was planned (Qb 200 mL/min; Qd 500 mL/min; countercurrent flow direction). Serum lithium levels decreased by 55% (2.10 mEq/L) during treatment, and the patient awoke, recovering a normal mental status. At the end of treatment, rebound of lithium concentration was observed at 4 hours from SLED end detected (from 2.1 to 2.5 mEq/L), with initial signs of mental deterioration. A second SLED (12 h) was performed, with the same operative parameters and, by the end of the second treatment, lithium concentration was 0.49 mEq/L. Afterward, mental status and renal function fully recovered and no rebound rebound was observed. The patient was discharged after 6 days. Conclusion SLED could represent a good therapeutic strategy to treat acute lithium intoxication, providing an initial rapid clearance with resolution of symptoms, and limiting major rebound.

Recovery of Expired Lithium Carbonate Tablets for LiFePO4/C Cathode

Various medicines may be overdue and invalid due to the untimely consumption. Herein, in order to reduce the resource waste and the environmental emission, expired lithium carbonate tablets were recycled in the form of LiFePO4/C powders via high temperature solid state reaction with the recovery of 85.8%. The obtained LiFePO4/C powders were investigated in terms of X-ray diffraction (XRD), scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDX), tap density measurement, electronic conductivity measurement, galvanostatic charge/discharge and cyclic voltammetry (CV). As expected, LiFePO4/C powders appeared as many nanoparticles with the particle size of about 300–700 nm. Furthermore, LiFePO4/C cathode maintained the reversible specific discharge capacity above 106.7 mAh/g at 2C for 400 cycles. The satisfactory results indicated high feasibility and provided a promising strategy to recycle the expired lithium carbonate tablets. Additionally, the techno-economic analysis of recovering the expired lithium carbonate tablets was performed, and the result indicated that the recycling cost of expired lithium carbonate tablets was much cheaper than that of commercial LiCO3 feedstock.

Population Pharmacokinetics of Lithium Carbonate in Young Male Healthy Chinese Volunteers.

Aim: To investigate the population pharmacokinetics (PK) model of lithium carbonate in young male healthy Chinese subjects. Methods: This study was conducted using a 2-period crossover design. 20 healthy male subjects received lithium carbonate tablets from 2 different Chinese pharmaceutical manufacturers. Plasma samples were obtained by blood sampling over 72 h in each period. Population PK analysis was performed using nonlinear mixed-effects model (NONMEM) software. The final models were validated using bootstrap and visual predictive check (VPC) approaches. Results: The final PK model was a two-compartment model. The population PK parameters, clearance (CL/F), apparent distribution volume of the central compartment (V2/F), inter-compartmental clearance (Q/F) and apparent distribution volume of the peripheral compartment (V3/F), were 9.39 L/h, 10.4 L, 22.1 L/h, and 216 L, respectively. Conclusion: Population PK models for lithium carbonate have been developed and considerable inter-subject variability was found in healthy young male Chinese subjects. It takes a long time to achieve the steady state in conventional therapy. This may provide guidelines for future use of lithium carbonate in China.

Calculating lithium doses in mental health

L is licensed for the acute and long-term management of mania in bipolar affective disorder (electronic Medicines Compendium, 2014). Lithium has a narrow therapeutic index, and the National Institute for Health and Care Excellence (NICE, 2014) recommends regular therapeutic drug monitoring and that health professionals should aim to achieve a lithium plasma concentration between 0.6 and 0.8 mmol/litre in patients initially treated with lithium. For those already on lithium and who have relapsed, a plasma concentration between 0.8–1.0 mmol/litre is recommended. If a patient’s lithium plasma concentration is suboptimal, they are at risk of relapsing with either a manic or depressive episode. Concentrations above the therapeutic range can result in lithium toxicity. Each preparation of lithium differs in its pharmacokinetic properties and the amount of lithium contained, therefore it is important that lithium is prescribed by brand name (Joint Formulary Committee (JFC), 2015). In addition, when substituting different preparations, it is important to ensure the conversion is done correctly. A patient is diagnosed with bipolar affective disorder and is currently prescribed Priadel (lithium carbonate) tablets 600 mg at night as prophylaxis of manic episodes. He has relapsed and is currently secreting his tablets, and the prescriber wishes to convert him to a liquid preparation. Priadel tablets contain 5.4 mmol of lithium per 200 mg tablet. Priadel liquid (lithium citrate) has a strength of 520 mg per 5 ml, and each 5 ml contains approximately 5.4 mmol (JFC, 2015). Priadel 200 mg tablets cost £2.30 per pack (containing 100 tablets), and 400 mg tablets cost £3.35 per pack (also containing 100 tablets). Priadel liquid costs £5.61 per 150 ml bottle (JFC, 2015).

Detoxication Treatment for Carbamazepine and Lithium Overdose

This article reports detoxication treatments of a case of combined overdose of carbamazepine and lithium in a 38-year-old female with bipolar disorder. She was brought to the emergency unit after the family found her unresponsive and lying near empty packages for carbamazepine (corresponded to 7.7 g) and lithium carbonate (corresponded to 6.6 g) tablets. On admission, her blood pressure, heart rate and respiratory rate were 80/55 mmHg, 90 per minute and 13 per minute, respectively. Her GCS was 3 (E1, M1, V1). She received gastric lavage after intratracheal intubation, followed by administration of activated charcoal via gastric tube, and a large volume (800 ml/h) of lactate Ringer's solution by intravenous infusion. The serum levels of carbamazepine and lithium approximately 5 h after ingestion were 56.0 mug/ml and 3.56 mEq/l, respectively. The carbamazepine overdose was mainly treated by a 3 h charcoal hemoperfusion (CHP). The CHP treatment decreased serum carbamazepine levels by approximately 30-40% as compared with the levels simulated by Bayesian analysis using 1-point or 2-points serum level(s) (without detoxication treatment). For lithium overdose continuous infusion of Ringer's solution was effective, which increased serum sodium gradually and facilitated the elimination of lithium. In conclusion, the treatments with CHP and continuous infusion of Ringer's solution were considered to be effective for detoxification of carbamazepine and lithium overdose, respectively, when compared with those drug levels without detoxication treatment that simulated by Bayesian analysis method.

Intoxicación aguda por comprimidos de liberación sostenida de carbonato de litio. A propósito de un caso clínico

To describe the case of a patient who ingested 50 sustained release lithium carbonate 400 mg tablets, and reached a late peak concentration above 3 mEq/L.A 32-year-old male with bipolar mood disorder ingested 50 sustained-release lithium carbonate tablets. Upon admission to the emergency room, a gastric wash was performed,from which several tablet remnants were obtained, as well as an intestinal lavage using activated carbon.good general status, no fever, blood pressure 160/90 mm Hg, no edemas. Neurologic, pulmonary, and cardiac examinations were normal. CBC and the chemistry panel were normal. The patient's psychopathological examination suggested a stable status with no apparent manifestations arising from a decompensated mood disorder. Five hours after his massive lithium ingestion the drug's plasma levels were 0.75 mEq/L. At 22 hours post-ingestion a chemistry panel was obtained, which showed serum creatinin at 1.38 mg/dL and a lithium plasma concentration of 3.15 mEq/L. A hemodyalisis trial was attempted for 4 hours. At 73 hours post-ingestion, lithium plasma levels were 0.6 mEq/L, that is, within therapeutic range. The patient was hemodynamically stable and serial blood tests were normal; he was discharged.Acute lithium intoxication with plasma levels above 3 mEq/l can be fatal or result in irreversible neurologicsequelae in almost one third of cases, with persistent cerebellar dysfunction in association with dementia of variable degree, andrenal, blood, and liver disturbances. Sustained-release tablets may prolong absorption and delay peak plasma concentrations. In such cases, therefore, it is recommended that drug plasma concentrations be monitored during 48-72 hours post-ingestion.

Photocured polymers in ion-selective electrode membranes Part 6: Photopolymerized lithium sensitive ion-selective electrodes for flow injection potentiometry

A photocured lithium ion-selective electrode, based on the ionophore N, N-dicyclohexyl- N′, N′-diisobutyl- cis-cyclohexane-1, 2-dicarboxamide (ETH 1810), was developed and evaluated. The robust nature of the photocured membrane made it ideally suitable for measurements in flow injection potentiometry within a linear range 0.1–10 −3 M, detection limit of 5 × 10 −4 M, and sample throughput of 150 h −1. The electrode was used successfully to determine lithium levels in pharmaceutical lithium carbonate tablets.

Intentional overdose by intravaginal insertion of lithium carbonate

To the Editor. —A 48-year-old woman with bipolar disorder and a history of borderline personality disorder and previous suicide attempts presented to an outlying emergency department, having recently vomited. She admitted to the ingestion, 60 minutes earlier, of 97 lithium carbonate tablets (immediate release, 300 mg each). Her vital signs were stable. Initial physical examination was normal except for mild lethargy and decreased patellar reflexes. An electrocardiogram showed mild T-wave flattening. Complete blood cell count and urinalysis were normal; a serum toxicology screen was negative except for lithium. Serum potassium was decreased at 3.3 mmol/L and serum lithium was 4.3 mmol/L. Gastric lavage revealed pill fragments. After stabilization, the patient was transported to our medical center's intensive care unit. On arrival the serum lithium level was 3.1 mmol/L. Potassium supplementation was provided along with intravenous fluids. Lithium levels rose to 3.5 mmol/L, and hemodialysis was instituted, resulting in a decrease

Single-dose bioavailability of two extended-release lithium carbonate products

The single-dose bioavailabilities of two extended-release lithium carbonate products and an immediate-release product were compared. Nonsmoking healthy volunteers ages 20-31 (n = 12) were randomly assigned to one of three groups and given three treatments, each separated by a one-week period. The treatments, which were given to each group in a different sequence, consisted of three 300-mg immediate-release lithium carbonate tablets (Lithotab), two 450-mg extended-release lithium carbonate tablets (Eskalith CR), and three 300-mg extended-release lithium carbonate tablets (Lithobid). Blood samples were collected just before drug administration and at intervals up to 48 hours afterward. Urine was collected for 96 hours. Plasma and urine lithium concentrations were determined by flame-emission spectrophotometry, and lithium pharmacokinetic values and the cumulative urinary excretion of lithium were computed. Mean maximum plasma lithium concentration (Cmax) differed significantly among all three lithium carbonate products. Eskalith CR produced a 40% lower Cmax and Lithobid a 25% lower Cmax than Lithotab; Lithobid produced a 23% higher Cmax than Eskalith CR. Lithotab had a significantly shorter mean time to maximum plasma lithium concentration than either extended-release product. Mean cumulative urinary excretion of lithium did not differ significantly among the three products. Two extended-release lithium carbonate products were not bioequivalent when given in single doses to healthy volunteers.

Formulation and in vitro-in vivo evaluation of sustained-release lithium carbonate tablets.

The release of lithium carbonate incorporated into polymethylmethacrylate, polyvinyl chloride, hydrogenated vegetable oil, and carbomer matrix tablets was studied in vitro. The formulation containing 10% carbomer showed a sustained-release profile comparable to that of a standard, commercially available, sustained-release preparation containing 400 mg lithium carbonate embedded in a composite material. In vivo the newly formulated and standard sustained-release lithium carbonate tablets were compared to an oral solution and conventional lithium carbonate tablets in 12 healthy subjects. These crossover studies showed that the sustained-release tablets produced a flatter serum concentration curve than the oral solution and conventional tablet, without loss of total bioavailability.

Effect of assay methodology on the prediction of lithium maintenance dosage.

Test dose methods have been used to predict the maintenance dosage of lithium carbonate tablets in bipolar patients. These methods require a lithium analytical method that is accurate to the second decimal place. Successful use of these test methods has employed the atomic absorption spectrophotometric method, yet many hospitals use a flame spectrophotometric method. We evaluated a two-point method to predict lithium maintenance dosages of slow-release lithium carbonate tablets in 20 bipolar patients using both assay methodologies. No clinically significant differences were found between the two sets of predictions, suggesting that either assay methodology has requisite sensitivity and accuracy for use in test dose predictions of lithium maintenance dosages.

Evaluation of a two-point method for prediction of lithium maintenance dosage.

A lithium test dose method, based on the two-point method of Perry et al. (1982), was evaluated in 20 patients for the prediction of maintenance dosage of slow-release lithium carbonate tablets. These predictions were compared with the predictions obtained from the dosing chart of Cooper et al. (1973). The two-point method accurately predicted the maintenance dosage within clinically acceptable limits, but dosages predicted from the dosing chart would have yielded much higher serum lithium concentrations.

The effect of media and other variables on the BP solution rate test for slow lithium carbonate tablets.

The British Pharmacopoeial test for assessing the solution rate of slow lithium carbonate tablets has been evaluated using 'controlled release' tablets containing 400 mg of lithium carbonate. No significant differences in lithium release were found when the volume of media used in the test was reduced from 250 ml to 200 ml, the final stage of the test in pH 6.8 phosphate buffer reduced from 5 to 3 h, the number of tablets in each thimble reduced from three to one, or the prescribed phosphate buffers replaced with phthalate and Tris, respectively. A four-fold increased concentration of phosphate in the phosphate buffers used resulted in a significant retardation in lithium solution rate. This was not attributable to an ionic strength effect but possibly to the formation of trilithium phosphate at the interface. Dissolution studies using the USP Basket Method showed a significantly slower release rate of one tablet into 900 ml of phosphate buffer compared with Tris buffer. This difference was markedly increased when three tablets were investigated in 200 ml of similar media. These differences were considered to be due to the formation of the much less soluble trilithium phosphate in the phosphate buffers.

Lithium and the kidney: Is one daily dose better than two?

Lithium is used in psychiatry both to treat manic episodes and to prophylax against mood swings in bipolar manic-depressive disorders. Lithium is still the only drug known with this latter, prophylactic, property, and the number of patients in ongoing lithium therapy is, therefore, very large. Since lithium is administered to patients for years, it is important that it be given in a way which leads to the best psychotropic effect with a minimum of side effects. This has been achieved in most psychiatric clinics by giving lithium in divided doses as a slow-release preparation. In recent years, however, results have shown that this may not be the best administration schedule, since evidence suggests that fewer renal side effects may be produced if lithium is given once daily (in the evening) in conventional lithium carbonate tablets. In this article, it is hypothesized that the therapeutic effect of lithium against mood swings is preserved, with fewer side effects, if lithium is given with larger intervals between doses, (e.g., every second or third day), provided that the drug is administered in such a way as to produce therapeutic lithium concentrations lasting for ten to 15 hours after each lithium intake. An administration schedule for this new method of lithium therapy is described.

A study of the use of lithium-6 enriched converters for the detection of neutrons with cellulose nitrate

Neutron converters containing 6Li can be used in conjunction with cellulose nitrate for the detection of thermal neutrons. This paper describes an evaluation of the effect of the degree of 6Li enrichment on such a system. Using six enrichments of lithium carbonate tablets, it was found that the sensitivity increased up to enrichment of approximately 63%, above which no significant improvement in sensitivity was observed.

The role of plasma volume, plasma renin and the sympathetic nervous system in the posture-induced decline in renal lithium clearance in man.

Excretion of lithium in urine was studied in 2 healthy males while recumbent and while upright, either walking or standing quietly. An oral dose of 24.3 mmol of Lit was taken as three lithium carbonate tablets 13 h before clearance tests. Renal lithium clearance decreased and lithium fractional reabsorption increased while upright. Standing immersed to the neck in water, which prevents the fall in plasma volume upon changing posture from recumbent to upright, prevented the fall in renal lithium clearance as well as the rise in lithium fractional reabsorption while upright. Oral doses of guanethidine (total dose of 200 mg) or oxprenolol (total dose of 140 mg) taken to prevent high levels of sympathetic nervous system activity and plasma renin, respectively, failed to prevent the fall in renal lithium clearance or the rise in lithium fractional reabsorption upon changing posture from recumbent to upright. The findings indicate that the fall in renal lithium clearance and the rise in lithium fractional reabsorption upon changing posture from recumbent to upright is related to the fall in plasma volume but not to high levels of sympathetic nervous system activity or plasma renin activity.

Lithium side effects in relation to dose and to levels and gradients of lithium in plasma

The relation between lithium dose, lithium concentrations, and lithium gradients in plasma and the side effects tremor, nausea, abdominal pains, and loose bowels was studied in 19 subjects. Rapidly dissolving lithium carbonate tablets were used. Tremor was related to higher doses, to higher concentrations, and to higher gradients of lithium in plasma. Nausea was related to higher gradients. Abdominal pain and loose bowels showed no relation to doses, levels or gradients. Concentrations of lithium were dose-dependent, while gradients were relatively independent of dose.

Comparison of side effects with coated lithium carbonate tablets and lithium sulphate preparations giving medium‐slow and slow‐release

Side effects with coated, rapidly dissolving lithium carbonate tablets, medium-slow-release and slow release lithium sulphate tablets, all administered twice a day, were compared in a double-blind, cross-over study in 27 patients who had only used lithium carbonate tablets. The relation between medication and meals was not standardized. The repidly dissolving tablets and the medium-slow-release tablets had a similar tendency to produce side effects, while slow-release tablets more often produced purgative side effects than the other two preparations did.

Comparison of plasma lithium levels and their interindividual variations with coated lithium carbonate tablets and a medium‐slow‐release lithium sulphate preparation (Lithionit Duretter®)

In a cross-over study in 10 subjects, rapidly dissolving coated lithium carbonate tablets and medium-slow-release lithium sulphate tablets were compared. Both preparations were administered twice a day. They gave similar post-absorptive concentrations of lithium in plasma and similar standard deviations of these concentrations. The medium-slow-release tablets gave smaller increases of lithium in plasma, and postponed the absorption peaks. They also gave less interindividual variation of lithium in plasma during the first few hours after administration.