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Lithium pharmacokinetics

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...
October 21, 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...
April 28, 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
C L Manuelian, E Albanell, M Rovai, G Caja, R Guitart
Lithium chloride (LiCl) is widely used for inducing conditioned taste aversion (CTA) so that livestock will reduce or avoid ingestion of toxic plants and graze groundcover mingled with valuable crops. However, pharmacokinetic studies of LiCl at effective CTA doses are lacking. With this aim, 6 Murciano-Grandina dairy does during late lactation and 6 dry Manchega dairy ewes were orally dosed with 200 and 225 mg LiCl/kg BW, respectively. Does were placed in metabolism cages whereas ewes were group fed in pens...
February 2015: Journal of Animal Science
Anne-Sophie Hanak, Lucie Chevillard, Souleiman El Balkhi, Patricia Risède, Katell Peoc'h, Bruno Mégarbane
Lithium-induced neurotoxicity may be life threatening. Three patterns have been described, including acute, acute-on-chronic, and chronic poisoning, with unexplained discrepancies in the relationship between clinical features and plasma lithium concentrations. Our objective was to investigate differences in plasma, erythrocyte, cerebrospinal fluid, and brain lithium pharmacokinetics using a multicompartmental approach in rat models mimicking the three human intoxication patterns. We developed acute (intraperitoneal administration of 185 mg/kg Li₂CO₃ in naive rats), acute-on-chronic (intraperitoneal administration of 185 mg/kg Li₂CO₃ in rats receiving 800 mg/l Li₂CO₃ in water during 28 days), and chronic poisoning models (intraperitoneal administration of 74 mg/kg Li₂CO₃ during 5 days in rats with 15 mg/kg K₂Cr₂O₇-induced renal failure)...
January 2015: Toxicological Sciences: An Official Journal of the Society of Toxicology
James Conor Kinahan, Aoife NiChorcorain, Sean Cunningham, Aideen Freyne, Colm Cooney, Siobhan Barry, Brendan D Kelly
OBJECTIVES: Polyuria increases the risk of dehydration and lithium toxicity in lithium-treated patients. Risk factors have been inconsistently described and the variance of this adverse effect remains poorly understood. This study aimed to establish independent risk factors for polyuria in a community, secondary-level lithium-treated sample of patients. METHODS: This was a cross-sectional study of the lithium-treated patients attending a general adult and an old age psychiatry service...
February 2015: Bipolar Disorders
Adam J Smith, Seol-Hee Kim, Jun Tan, Kevin B Sneed, Paul R Sanberg, Cesar V Borlongan, R Douglas Shytle
Despite its narrow therapeutic window, lithium is still regarded as the gold standard comparator and benchmark treatment for mania. Recent attempts to find new drugs with similar therapeutic activities have yielded new chemical entities. However, these potential new drugs have yet to match the many bioactivities attributable to lithium's efficacy for the treatment of neuropsychiatric diseases. Consequently, an intense effort for re-engineering lithium therapeutics using crystal engineering is currently underway...
2014: RSC Advances
Yu-Yuan Chiu, Larry Ereshefsky, Sheldon H Preskorn, Nagaraju Poola, Antony Loebel
BACKGROUND: To evaluate potential drug-drug interactions with the atypical antipsychotic lurasidone. METHODS: Seven phase I studies were conducted to investigate the effects of repeated dosing of ketoconazole, diltiazem, rifampin, or lithium on the pharmacokinetics (PK) of single oral doses of lurasidone, or the effects of repeated dosing of lurasidone on the PK of digoxin, midazolam, or the oral contraceptive norgestimate/ethinyl estradiol. Two 6-week, phase III studies included evaluation of the potential for interaction between lurasidone and lithium or valproate...
2014: Drug Metabolism and Drug Interactions
Kristina M Deligiannidis, Nancy Byatt, Marlene P Freeman
OBJECTIVE: Pharmacotherapy for mood disorders during pregnancy is often complicated by pregnancy-related pharmacokinetic changes and the need for dose adjustments. The objectives of this review are to summarize the evidence for change in perinatal pharmacokinetics of commonly used pharmacotherapies for mood disorders, discuss the implications for clinical and therapeutic drug monitoring (TDM), and make clinical recommendations. METHODS: The English-language literature indexed on MEDLINE/PubMed was searched for original observational studies (controlled and uncontrolled, prospective and retrospective), case reports, and case series that evaluated or described pharmacokinetic changes or TDM during pregnancy or the postpartum period...
April 2014: Journal of Clinical Psychopharmacology
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