A population PK model for citalopram and its major metabolite, N-desmethyl citalopram, in rats
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| 024 | 7 | 0 | |a 10.1007/s10928-015-9448-7 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s10928-015-9448-7 | ||
| 245 | 0 | 2 | |a A population PK model for citalopram and its major metabolite, N-desmethyl citalopram, in rats |h [Elektronische Daten] |c [Nieves Velez de Mendizabal, Kimberley Jackson, Brian Eastwood, Steven Swanson, David Bender, Stephen Lowe, Robert Bies] |
| 520 | 3 | |a A population PK model was developed in order to simultaneously describe citalopram and its major metabolite, n-desmethyl citalopram, plasma concentrations in two different strain of rats after intravenous (IV) and oral (PO) administration of citalopram. Citalopram was administered to Sprague-Dawley (SD) rats at doses: 0.3, 1, 3, and 10mg/kg IV and 10mg/kg PO. The compound was dosed orally to Wistar rats at doses: 0.3, 1, 3, 10, 30 and 60mg/kg. Plasma samples were collected for citalopram and metabolite. Pharmacokinetic analyses were conducted using NONMEM 7.2. Values below the quantification limit (BLQ <0.1ng/mL) were included in the analyses and treated as censored information. The disposition of citalopram was best described by a 3-compartment model and its desmethyl metabolite by a 2-compartment model. Several models for the absorption rate were explored (e.g. first, zero order and combined first and zero order absorption, Michaelis-Menten, lag time) in combination with dose and/or time dependent covariate effects. Dose dependent oral bioavailability properties were also identified in this analysis. Citalopram IV clearance and metabolite formation rate were adequately described as linear processes. Metabolite clearance was adequately described using a Michaelis-Menten clearance with different parameters depending on the strain. This analysis demonstrates a very complex absorption/metabolism process explaining the highly non-linear pharmacokinetics observed across all the doses. This is the first combined parent/metabolite population PK analysis in both SD and Wistar rats over a wide range of IV and PO dosages for citalopram, a compound that exhibits highly nonlinear oral pharmacokinetics in rats. | |
| 540 | |a Springer Science+Business Media New York, 2015 | ||
| 690 | 7 | |a Citalopram |2 nationallicence | |
| 690 | 7 | |a N-desmethyl citalopram |2 nationallicence | |
| 690 | 7 | |a Metabolite |2 nationallicence | |
| 690 | 7 | |a NONMEM |2 nationallicence | |
| 690 | 7 | |a PK : Pharmacokinetic |2 nationallicence | |
| 690 | 7 | |a PO : per os (oral administration) |2 nationallicence | |
| 690 | 7 | |a IV : Intravenous |2 nationallicence | |
| 690 | 7 | |a SD : Sprague-Dawley |2 nationallicence | |
| 690 | 7 | |a BLQ : Below the limit of quantification |2 nationallicence | |
| 690 | 7 | |a SSRI : Selective serotonin reuptake inhibitor |2 nationallicence | |
| 690 | 7 | |a MM : Michaelis-Menten |2 nationallicence | |
| 700 | 1 | |a Velez de Mendizabal |D Nieves |u Global PK/PD and Pharmacometrics, Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, 46285, Indianapolis, IN, USA |4 aut | |
| 700 | 1 | |a Jackson |D Kimberley |u Global PK/PD and Pharmacometrics, Eli Lilly and Company, Windlesham, UK |4 aut | |
| 700 | 1 | |a Eastwood |D Brian |u Global Statistical Sciences, Eli Lilly and Company, Windlesham, UK |4 aut | |
| 700 | 1 | |a Swanson |D Steven |u Drug Disposition, Eli Lilly and Company, Indianapolis, IN, USA |4 aut | |
| 700 | 1 | |a Bender |D David |u Product Design and Developability, Eli Lilly and Company, Indianapolis, IN, USA |4 aut | |
| 700 | 1 | |a Lowe |D Stephen |u Lilly-NUS Centre for Clinical Pharmacology, Eli Lilly and Company, Singapore, Singapore |4 aut | |
| 700 | 1 | |a Bies |D Robert |u Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, USA |4 aut | |
| 773 | 0 | |t Journal of Pharmacokinetics and Pharmacodynamics |d Springer US; http://www.springer-ny.com |g 42/6(2015-12-01), 721-733 |x 1567-567X |q 42:6<721 |1 2015 |2 42 |o 10928 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s10928-015-9448-7 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s10928-015-9448-7 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Velez de Mendizabal |D Nieves |u Global PK/PD and Pharmacometrics, Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, 46285, Indianapolis, IN, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Jackson |D Kimberley |u Global PK/PD and Pharmacometrics, Eli Lilly and Company, Windlesham, UK |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Eastwood |D Brian |u Global Statistical Sciences, Eli Lilly and Company, Windlesham, UK |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Swanson |D Steven |u Drug Disposition, Eli Lilly and Company, Indianapolis, IN, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bender |D David |u Product Design and Developability, Eli Lilly and Company, Indianapolis, IN, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Lowe |D Stephen |u Lilly-NUS Centre for Clinical Pharmacology, Eli Lilly and Company, Singapore, Singapore |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Bies |D Robert |u Division of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Pharmacokinetics and Pharmacodynamics |d Springer US; http://www.springer-ny.com |g 42/6(2015-12-01), 721-733 |x 1567-567X |q 42:6<721 |1 2015 |2 42 |o 10928 | ||