Abstract:
PURPOSE:Lithium (Li), the first-line treatment of bipolar disorder, was first developed as an immediate-release form with a routine therapeutic drug monitoring 12 h after the last dose. In Europe, the most commonly prescribed form is a sustained release (srLi). Yet no pharmacokinetics (PK) study has been published of srLi, administered once a day, in adults. The present study describes srLi PK in the serum and erythrocytes of bipolar patients. METHODS:To assess srLi PK, we studied prospectively 17 French bipolar patients on a median dose of 1000 mg (600-1600) for at least 2 years. Serum (S), erythrocyte (E) concentrations, and urinary (U) amount were collected over 8 h after 15 days of morning intake using monitoring electronic medical system (MEMs). Population PK parameters were estimated using the SAEM algorithm (MONOLIX 4.3.3 software). RESULTS:Using a population approach, we built a PK population model of srLi including one S compartment (VS = 23.0 L, ClS = 1.21 L h-1), one E compartment (VE = 64.7 L, ClSE = 3.63 L h-1, ClES = 9.46 L h-1), and one U compartment (F = 0.62) and estimate the ratio of concentrations to Li in E over S at 0.38 with 27% between-subject variability. CONCLUSION:This is a PK model of srLi once a day in bipolar patients using a population approach simultaneously describing Li concentrations in serum, erythrocytes, and urine which provide an estimate of the ratio of concentration in erythrocyte over serum and its between-subject variability (BSV).
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Couffignal C,Bertrand J,Sportiche S,Jarroir M,El Balkhi S,Djebrani-Oussedik N,Poupon J,Declèves X,Mentré F,Bellivier Fdoi
10.1007/s00228-018-2605-3subject
Has Abstractpub_date
2019-04-01 00:00:00pages
519-528issue
4eissn
0031-6970issn
1432-1041pii
10.1007/s00228-018-2605-3journal_volume
75pub_type
杂志文章abstract:OBJECTIVE:Theophylline is metabolized to 1,3-dimethyluric acid (1,3-DMU), 3-methylxanthine, and 1-methylxanthine by CYP1A2 and partly by CYP2E1. Because 1,3-DMU is the major metabolite of theophylline, the 1,3-DMU/theophylline ratio is viewed as a good indicator of theophylline metabolic clearance. Here, we investigate...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章
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journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 临床试验,杂志文章
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abstract::Propranolol (P) and all of its major known metabolites were found in maternal plasma, cord plasma and neonatal plasma in 10 women at term, irrespective of the P doses administered and the time elapsed (up to 15 h) between administration of the last P dose and delivery. The ratios of cord plasma to simultaneous materna...
journal_title:European journal of clinical pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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