Routine Therapeutic Drug Monitoring in Patients Treated with 10-360 mg/day Citalopram
Autor: | Brigitte Woggon, Marlyse Brawand-Amey, Yves Le Bloc'h, Jacques Spagnoli, Pierre Baumann, Hansjörg Weissenrieder, Chin B. Eap |
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Rok vydání: | 2003 |
Předmět: |
Adult
Male medicine.medical_specialty Adolescent Dose Citalopram Mixed Function Oxygenases Pharmacokinetics Internal medicine Blood plasma medicine Humans Pharmacology (medical) In patient Child Aged Aged 80 and over Pharmacology Didemethylcitalopram Plasma samples medicine.diagnostic_test Chemistry business.industry Middle Aged Cytochrome P-450 CYP2C19 Endocrinology Cytochrome P-450 CYP2D6 Therapeutic drug monitoring Antidepressive Agents Second-Generation Female Aryl Hydrocarbon Hydroxylases Drug Monitoring Nuclear medicine business medicine.drug |
Zdroj: | Therapeutic Drug Monitoring. 25:600-608 |
ISSN: | 0163-4356 |
Popis: | From data collected during routine TDM, plasma concentrations of citalopram (CIT) and its metabolites demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) were measured in 345 plasma samples collected in steady-state conditions. They were from 258 patients treated with usual doses (20-60 mg/d) and from patients medicated with 80-360 mg/d CIT. Most patients had one or several comedications, including other antidepressants, antipsychotics, lithium, anticonvulsants, psychostimulants and somatic medications. Dose-corrected CIT plasma concentrations (C/D ratio) were 2.51 +/- 2.25 ng mL-1 mg-1 (n = 258; mean +/- SD). Patients65 years had significantly higher dose-corrected CIT plasma concentrations (n = 56; 3.08 +/- 1.35 ng mL-1 mg-1) than younger patients (n = 195; 2.35 +/- 2.46 ng mL-1 mg-1) (P = 0.03). CIT plasma concentrations in the generally recommended dose range were [mean +/- SD, (median)]: 57 +/- 64 (45) ng/mL (10-20 mg/d; n = 64), 117 +/- 95 (91) ng/mL (21-60 mg/d; n = 96). At higher than usual doses, the following concentrations of CIT were measured: 61-120 mg/d CIT, 211 +/- 103 (190) ng/mL (n = 93); 121-200 mg/d: 339 +/- 143 (322) ng/mL (n = 70); 201-280 mg/d: 700 +/- 408 (565) ng/mL (n = 18); 281-360 mg/d: 888 +/- 620 (616) ng/mL (n = 4). When only one sample per patient (at the highest daily dose if repeated dosages) is considered, there is a linear and significant correlation (n = 48, r = 0.730; P0.001) between daily dose (10-200 mg/d) and CIT plasma concentrations. In experiments with dogs, DDCIT was reported to affect the QT interval when present at concentrations300 ng/mL. In this study, DDCIT concentration reached 100 ng/mL in a patient treated with 280 mg/d CIT. Twelve other patients treated with 140-320 mg/d CIT had plasma concentrations of DDCIT within the range 52-73 ng/mL. In a subgroup comprised of patients treated withor =160 mg/d CIT and with CIT plasma concentrationsor =300 ng/mL, and patients treated withor =200 mg/d CIT and CIT plasma concentrationsor = 600 ng/mL, the enantiomers of CIT and DCIT were also analyzed. The highest S-CIT concentration measured in this subgroup was 327 ng/mL in a patient treated with 140 mg/d CIT, but the highest S-CIT concentration (632 ng/mL) was measured in patient treated with 360 mg/d CIT. In conclusion, there is a highly linear correlation between CIT plasma concentrations and CIT doses, well above the usual dose range. |
Databáze: | OpenAIRE |
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