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Lithium pharmacokinetics

Anne-Sophie Hanak, Lucie Chevillard, Rodolphe Lebeau, Patricia Risède, Jean-Louis Laplanche, Nadia Benturquia, Bruno Mégarbane
Severity of lithium poisoning depends on the ingested dose, previous treatment duration and renal function. No animal study has investigated neurobehavioral differences in relation to the lithium poisoning pattern observed in humans, while differences in lithium pharmacokinetics have been reported in lithium-pretreated rats mimicking chronic poisonings with enhanced brain accumulation in rats with renal failure. Our objectives were: 1)-to investigate lithium-related effects in overdose on locomotor activity, anxiety-like behavior, spatial recognition memory and anhedonia in the rat; 2)-to model the relationships between lithium-induced effects on locomotion and plasma, erythrocyte, cerebrospinal fluid and brain concentrations previously obtained according to the poisoning pattern...
March 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Irosh Fernando
OBJECTIVE: In cases of drug overdose, clinicians often find it challenging to predict serum drug level and decide the optimum time for recommencing the overdosed drug. METHOD: This paper describes how to predict serum drug level using the principles of pharmacokinetics. RESULTS: The proposed method and recommencement of the overdosed drug is demonstrated using a clinical case of lithium overdose. CONCLUSION: The proposed method can assist clinicians in predicting serum drug levels and deciding the optimum time for recommencing the overdosed drug safely...
February 1, 2017: Australasian Psychiatry: Bulletin of Royal Australian and New Zealand College of Psychiatrists
Eric H Decloedt, Maia Lesosky, Gary Maartens, John A Joska
BACKGROUND: The prevalence of bipolar disorder in HIV-infected patients is higher than the general population. Lithium is the most effective mood stabiliser, while tenofovir disoproxil fumarate (TDF) is frequently used as part of combination antiretroviral therapy (ART). Both TDF and lithium are associated with renal tubular toxicity, which could be additive, or a pharmacokinetic interaction may occur at renal transporters with a decrease in TDF elimination. OBJECTIVE: We report on the change in estimated glomerular filtration rate (eGFR) using the modification of diet in renal disease formula in participants who received ART including TDF and were enrolled in a 24 week randomised trial of lithium versus placebo in patients with HIV-associated neurocognitive impairment...
February 4, 2017: AIDS Research and Therapy
Yuichi Uwai, Masashi Matsumoto, Tatsuya Kawasaki, Tomohiro Nabekura
AIMS: Lithium is administered for treating bipolar disorders and is mainly excreted into urine. Nonsteroidal anti-inflammatory drugs inhibit this process. In this study, we examined the enantioselective effect of flurbiprofen on the disposition of lithium in rats. METHODS: Pharmacokinetic experiments with lithium were performed. RESULTS: Until 60 min after the intravenous administration of lithium chloride at 30 mg/kg as a bolus, 17.8% of lithium injected was recovered into the urine...
2017: Pharmacology
Isabel Pérez-Castelló, Víctor Mangas-Sanjuan, Ignacio González-García, Isabel Gonzalez-Alvarez, Marival Bermejo, Jose Luis Marco-Garbayo, Iñaki F Trocóniz
Population pharmacokinetic analysis of lithium during therapeutic drug monitoring and drug compliance assessment was performed in 54 patients and 246 plasma concentrations levels were included in this study. Patients received several treatment cycles (1-9) and one plasma concentration measurement for each patient was obtained always before starting next cycle (pre-dose) at steady state. Data were analysed using the population approach with NONMEM version 7.2. Lithium measurements were described using a two-compartment model (CL/F=0...
December 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Azza A K El-Sheikh, Maha Y Kamel
To investigate the effect of Ginsenoside-Rb1 (GRb1) on lithium (Li(+))-induced toxicity, GRb1 was given to rats orally (100mg/kg) for 14days. In independent groups, lithium chloride (4meq/kg/day i.p.) was administered at day 4 of the experiment for 10days, with or without GRb1. Li(+) caused significant deterioration of behavioral responses including righting reflex, spontaneous motor activity and catalepsy. Li(+) also caused distortion in normal renal, cerebral and cerebellum architecture and significantly worsened all kidney functional parameters tested compared to control...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Paolo Girardi, Roberto Brugnoli, Giovanni Manfredi, Gabriele Sani
Lithium has been a gold standard in the treatment of bipolar disorder (BD) for several decades. Despite a general reduction in the use of lithium over the past several years, it is effective in the management of both manic and depressive episodes in BD and continues to be recommended as a first-line mood stabilizer. This review provides an overview of the pharmacology of lithium and highlights its clinical profile in the management of BD, focusing on the potential advantages of prolonged-release (PR) versus immediate-release (IR) formulations of lithium...
December 2016: Drugs in R&D
Onyebuchi E Okosieme, John H Lazarus
INTRODUCTION: Graves' hyperthyroidism is associated with significant morbidity and mortality risk. The thionamides, methimazole, its pro-drug derivative carbimazole, and propylthiouracil, remain a cornerstone of management. Yet despite decades of use, optimal strategies for maximising treatment response and curtailing adverse effect risk remains uncertain. AREAS COVERED: We reviewed the current literature on the evidence based medical management of Graves' disease...
October 2016: Expert Opinion on Pharmacotherapy
Cornelia B Landersdorfer, Robert L Findling, Jean A Frazier, Vivian Kafantaris, Carl M J Kirkpatrick
BACKGROUND: Lithium is a well-established treatment for bipolar I disorder in adults. However, there is a paucity of information on its pharmacokinetics/pharmacodynamics in children and adolescents. We aimed to develop the first lithium dosage regimens based on population pharmacokinetics/pharmacodynamics for paediatric patients. METHODS: Lithium concentrations, Young Mania Rating Scale (YMRS) and Clinical Global Impressions-Improvement (CGI-I) scores over 24 weeks were available from 61 paediatric patients with bipolar I disorder...
July 8, 2016: Clinical Pharmacokinetics
Evelyn A Jähne, Chethan Sampath, Veronika Butterweck, Matthias Hamburger, Mouhssin Oufir
An UPLC-MS/MS method for the quantification of indirubin in lithium heparinized rat plasma was developed and validated according to current international guidelines. Indirubin was extracted from rat plasma by using Waters Ostro™ pass-through sample preparation plates. The method was validated with a LLOQ of 5.00ng/mL and an ULOQ of 500ng/mL. The calibration curve was fitted by least-square quadratic regression, and a weighting factor of 1/X was applied. Recoveries of indirubin and I.S. were consistent and ≥75...
September 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
W Yu, X Sun, Y Li, M Li, K Wang, H Li
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...
September 2016: Pharmacopsychiatry
Grace Chen, George G Nomikos, John Affinito, Zhen Zhao
INTRODUCTION: Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination. OBJECTIVE: These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vortioxetine and ethanol, diazepam, or lithium. METHODS: This series of phase I studies included healthy men and women (only men in the lithium study) aged 18-45 years...
September 2016: Clinical Pharmacokinetics
Scott A Churchman, John A Moss, Marc M Baum
An ion chromatographic method with conductivity detection for the precise and accurate analysis of lithium ions in phosphate-buffered saline, used as a cervicovaginal lavage (CVL) fluid, was developed and validated. The lithium ion dilution factor during the CVL is used to calculate the volume of cervicovaginal fluid (CVF) collected. Initial CVL Li(+) concentrations of 1mM and 10mM were evaluated. The method is robust, practical, and afforded an accurate measurement (5% of the measurement, or better) at 24μL of vaginal fluid simulant collected per mL of CVL fluid, as low as 5μLmL(-1) using 10mM Li(+) with a measurement accuracy of 6...
April 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Patrick R Finley
Lithium has been used for the management of psychiatric illnesses for over 50 years and it continues to be regarded as a first-line agent for the treatment and prevention of bipolar disorder. Lithium possesses a narrow therapeutic index and comparatively minor alterations in plasma concentrations can have significant clinical sequelae. Several drug classes have been implicated in the development of lithium toxicity over the years, including diuretics and non-steroidal anti-inflammatory compounds, but much of the anecdotal and experimental evidence supporting these interactions is dated, and many newer medications and medication classes have been introduced during the intervening years...
August 2016: Clinical Pharmacokinetics
Yunhui Chen, Youming Lu, Yong Yang, Xiaoyan Chen, Liang Zhu, Dafang Zhong
Ginsenoside compound K (GCK), the main metabolite of protopanaxadiol constituents of Panax ginseng, easily produces alkali metal adduct ions during mass spectrometry particularly with lithium. Accordingly, we have developed a rapid and sensitive liquid chromatography-tandem mass spectrometric method for analysis of GCK in human plasma based on formation of a lithium adduct. The analyte and paclitaxel (internal standard) were extracted from 50 µL human plasma using methyl tert-butyl ether. Chromatographic separation was performed on a Phenomenex Gemini C18 column (50 mm×2...
September 2015: Acta Pharmaceutica Sinica. B
R Machado-Vieira, M C Otaduy, M V Zanetti, R T De Sousa, V V Dias, C C Leite, O V Forlenza, G F Busatto, J C Soares, W F Gattaz
OBJECTIVE: The objective of this study was to evaluate brain lithium levels using (7) Li magnetic resonance spectroscopy after 6 weeks of lithium therapy in bipolar depression to test the hypothesis that brain and plasma lithium are correlated. It was also tested whether responders and remitters have different pharmacokinetics, blood and brain lithium levels (ratio) compared with those presenting suboptimal antidepressant improvement. METHOD: Twenty-three patients with bipolar disorder (I and II) during depressive episodes were included and followed up for 6 weeks at the University of Sao Paulo using flexible dose of lithium (450-900 mg/day)...
March 2016: Acta Psychiatrica Scandinavica
Yuichi Uwai, Misato Tsuge, Yuta Tokai, Tatsuya Kawasaki, Tomohiro Nabekura
AIMS: Lithium is effective in the treatment for bipolar disorder and is known to influence renal functions. The purpose of this study was to examine the effects of lithium on the renal organic anion transport system. METHODS: Pharmacokinetic experiments using rats and Western blotting were conducted. RESULTS: Until 60 min after the intravenous injection of phenolsulfonphthalein, a typical substrate of the renal organic anion transporters, as a bolus, 41...
2015: Pharmacology
Christoph Hiemke
Therapeutic drug monitoring (TDM) is a valuable tool for tailoring the dosage of the prescribed medication(s) to the individual pharmacokinetic characteristics of a patient. In psychiatry and neurology, however, proven evidence that TDM should be used for treatment with the multiple neuropsychiatric medications is restricted to few compounds. Well-designed clinical trials on medical and economic benefits of TDM are rare. The use of TDM is limited in most countries to few antiepileptics, especially carbamazepine, phenobarbital and phenytoin, some mood stabilizers, especially lithium and valproic acid, some antidepressants, especially tricyclic antidepressants and some antipsychotics, primarily clozapine because these drugs have a narrow therapeutic index...
2016: Current Drug Delivery
O A Gromova, L Yu Torshin, I V Gogoleva, A V Pronin, E V Stelmashuk, N K Isaev, E E Genrikhs, V I Demidov, A Yu Volkov, G L Khaspekov, O P Alexandrova
OBJECTIVE: To study the synergism between neuropeptides and lithium ions. MATERIAL AND METHODS: An experimental model of stroke (chronic bilateral occlusion of the common carotid arteries in rats), neuronal culture studies, histomorphological analyses, determination of micronutrient profile of brain substrates were used. RESULTS: A complex of experimental studies revealed that the effect of cerebrolysin is influenced by the synergism between lithium ions and the neuropeptide contentof this drug...
2015: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Min Liao, Xiao Chen, Jiefeng Chen, Mengping Liu, Junyi Wang, Zuanguang Chen, Zhiyong Xie, Meicun Yao
An original and sensitive ultraperformance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method for the determination of pseudoprotodioscin (PPD) in rat plasma was developed and validated. Digitoxin was applied as an internal standard. Plasma samples were processed by acetonitrile-mediated plasma protein precipitation and chromatographed using a step gradient program on a C18 column (2.1×50mm i.d., 1.7μm). The mobile phase was comprised of acetonitrile and 0.1mmolL(-1) aqueous lithium acetate mixed with 0...
July 15, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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