Bioavailability of lithium from lithium citrate syrup versus conventional lithium carbonate tablets

Guelen, P. J. M.; Janssen, Τ.; Witte, T. C. M. de; Vree, T. B.; Benson, Kellyi K

doi:10.1002/bdd.2510130704

Cited by 14 publications

(5 citation statements)

References 4 publications

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“…Lithium citrate, available in the commercial formulation Litarex, was approved for use in the late 1970s (Fyro, 1975). Studies exploring its efficacy have reported a range of different outcomes, from no difference relative to Li 2 CO 3 (Guelen et al., 1992; Shelley & Silverstone, 1986), to significant reductions in peak serum lithium levels (Tyrer et al., 1982). No major differences in side‐effect profile have been noted (Sachs et al., 2000; Shelley & Silverstone, 1986).…”

Section: Alternative Lithium Salt Formulationsmentioning

confidence: 99%

Lithium orotate: A superior option for lithium therapy?

Pacholko

Bekar

2021

Brain and Behavior

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Bipolar disorder (BD) poses a significant public health concern, with roughly onequarter of sufferers attempting suicide. BD is characterized by manic and depressive mood cycles, the recurrence of which can be effectively curtailed through lithium therapy. Unfortunately, the most frequently employed lithium salt, lithium carbonate (Li 2 CO 3 ), is associated with a host of adverse health outcomes following chronic use: these unwanted effects range from relatively minor inconveniences (e.g., polydipsia and polyuria) to potentially major complications (e.g., hypothyroidism and/or renal impairment). As these undesirable effects can limit patient compliance, an alternative lithium compound with a lesser toxicity profile would dramatically improve treatment efficacy and outcomes. Lithium orotate (LiC 5 H 3 N 2 O 4 ; henceforth referred to as LiOr), a compound largely abandoned since the late 1970s, may represent such an alternative. LiOr is proposed to cross the blood-brain barrier and enter cells more readily than Li 2 CO 3 , which will theoretically allow for reduced dosage requirements and ameliorated toxicity concerns. This review addresses the controversial history of LiOr, complete with discussions of experimental and clinical efficacy, putative mechanisms of action, adverse effects, and its potential future in therapy.

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Section: Alternative Lithium Salt Formulationsmentioning

confidence: 99%

Lithium orotate: A superior option for lithium therapy?

Pacholko

Bekar

2021

Brain and Behavior

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“…Other studies focused on comparing bioavailability of different lithium preparations, e.g. lithium carbonate versus lithium citrate (Guelen et al, 1992) or extended and immediate release lithium formulations (Arancibia et al, 1986). Estimated bioavailability was calculated to range from 60-90%, depending on formulation (Ware et al, 2016), which is assumed to be equivalent in humans (Grandjean and Aubry, 2009).…”

Section: Effect Of Lithium Administration On Plasma Lithium Levels Anmentioning

confidence: 99%

Contribution of NHE3 and dietary phosphate to lithium pharmacokinetics

Thomas

Xue

Rieg

et al. 2019

European Journal of Pharmaceutical Sciences

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Lithium is one of the mainstays for the treatment of bipolar disorder despite its side effects on the endocrine, neurological, and renal systems. Experimentally, lithium has been used as a measure to determine proximal tubule reabsorption based on the assumption that lithium and sodium transport go in parallel in the proximal tubule. However, the exact mechanism by which lithium is reabsorbed remains elusive. The majority of proximal tubule sodium reabsorption is directly or indirectly mediated by the sodium-hydrogen exchanger 3 (NHE3). In addition, sodium-phosphate cotransporters have been implicated in renal lithium reabsorption. In order to better understand the role of sodium-phosphate cotransporters involved in lithium (re)absorption, we studied lithium pharmacokinetics in: i) tubule-specific NHE3 knockout mice (NHE3 loxloxPax8Cre), and ii) mice challenged with low or high phosphate diets. Intravenous or oral administration of lithium did not result in differences in lithium bioavailability, half-life, maximum plasma concentrations, area under the curve, lithium clearance, or urinary lithium/creatinine ratios between control and NHE3 loxloxPax8Cre mice. After one week of dietary phosphate challenges, lithium bioavailability was ~30% lower on low versus high dietary phosphate, possibly the consequence of a smaller area under the curve after oral administration. This was associated with lower lithium clearance after oral administration and lower urinary lithium/creatinine ratios on low versus high dietary phosphate. Collectively, renal NHE3 does not play a role in lithium pharmacokinetics; however, dietary phosphate could have an indirect effect on lithium bioavailability and lithium disposition.

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“…Only lithium carbonate (LICA) and lithium citrate integrate the British National Formulary (BNF). Although the bioavailability of the two preparations is similar, 15 peak lithium concentration is 10% higher in LICA preparations 16 thus, this is most widely prescribed. 17 Lithium does not undergo metabolism and is almost exclusively excreted by the kidneys (renal clearance values of 10-40 mL/minute, strongly correlated with renal function).…”

Section: Lithiummentioning

confidence: 99%

At Physiologically Relevant Concentrations, Valproic Acid and Lithium Carbonate Reduce Oxidative Stress in Human Astrocytoma Cells

Rodrigues

Chichger

2019

EMJ Neurol

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Background: The pathophysiology of bipolar disorder is largely unknown; however, recent studies have suggested that metabolic dysfunction, particularly at the mitochondrial level, may represent a previously unexplored pathway. Lithium carbonate, valproic acid, and a combination of these represent the mainstay of treatment for bipolar disorder; however, the mechanisms underpinning the drugs’ clinical efficacy are not well characterised. At present, such mechanistic studies use concentrations which widely differ from the known bioavailability, thus, there is a need to establish the effect of lithium carbonate, valproic acid, and combination therapy at physiologically relevant doses. Methods: Human astrocytoma 1321N1 cells were treated for 4, 24, and 48 hours. The MTT method was used to detect cytotoxicity upon drug treatment. Reactive oxygen species (ROS) production was quantified by dichlorofluorescin diacetate fluorescence. Results: Upon H2O2-induced cellular stress, cell viability was significantly reduced; however, lithium exhibited a protective effect. In the absence of the stressor, the drugs had no negative effect on 1321N1 cellular viability. All the drug treatments exhibited protection against H2O2-induced ROS accumulation with lithium, bringing it closer to the control baseline. Conclusion: The findings contribute to the understanding of the drugs’ biological effects, particularly as oxidative stress reducers. Furthermore, it highlights the need for research using comparable physiologically relevant models. This may advance the discovery of diagnostic biomarkers and new research approaches to the diagnosis of bipolar disorder.

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Bioavailability of lithium from lithium citrate syrup versus conventional lithium carbonate tablets

Cited by 14 publications

References 4 publications

Lithium orotate: A superior option for lithium therapy?

Lithium orotate: A superior option for lithium therapy?

Contribution of NHE3 and dietary phosphate to lithium pharmacokinetics

At Physiologically Relevant Concentrations, Valproic Acid and Lithium Carbonate Reduce Oxidative Stress in Human Astrocytoma Cells

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