AIMS: To investigate the pharmacokinetics (PK) of sertraline in overdose and the effect of single dose activated charcoal (SDAC). METHODS: Patients presenting to a toxicology unit with sertraline overdoses had demographic and clinical information recorded, and serial serum collected for measurement of sertraline concentrations. Monolix® version 4.2 was used to develop a population PK model of sertraline overdose and the effect of SDAC. Uncertainty in dose time was accounted for by shifting dose time using lag time with between subject variability (BSV). BSV on relative fraction absorbed was used to model uncertainty in dose. RESULTS: There were 77 timed sertraline concentrations measured in 28 patients with sertraline overdoses with a median dose of 1550 mg (250-5000 mg). SDAC was given to seven patients between 1.5 and 4 h post-overdose. A one compartment model with lag time of 1 h and first order input and elimination adequately described the data. Including BSV on both lag time and relative fraction absorbed improved the model. The population PK parameter estimates for absorption rate constant, volume of distribution and clearance were 0.895 h(-1) , 5340 l and 130 l h(-1) , respectively. The calculated half-life of sertraline following overdose was 28 h (IQR 19.4-30.6h). When given up to 4 h post-overdose, SDAC significantly increased the clearance of sertraline by a factor of 1.9, decreased the area under the curve and decreased the maximum plasma concentration (Cmax ). CONCLUSIONS: Sertraline had linear kinetics in overdose with parameter values similar to those in therapeutic use. SDAC is effective in increasing clearance when given 1.5 to 4 h post-overdose.
AIMS: To investigate the pharmacokinetics (PK) of sertraline in overdose and the effect of single dose activated charcoal (SDAC). METHODS:Patients presenting to a toxicology unit with sertraline overdoses had demographic and clinical information recorded, and serial serum collected for measurement of sertraline concentrations. Monolix® version 4.2 was used to develop a population PK model of sertralineoverdose and the effect of SDAC. Uncertainty in dose time was accounted for by shifting dose time using lag time with between subject variability (BSV). BSV on relative fraction absorbed was used to model uncertainty in dose. RESULTS: There were 77 timed sertraline concentrations measured in 28 patients with sertraline overdoses with a median dose of 1550 mg (250-5000 mg). SDAC was given to seven patients between 1.5 and 4 h post-overdose. A one compartment model with lag time of 1 h and first order input and elimination adequately described the data. Including BSV on both lag time and relative fraction absorbed improved the model. The population PK parameter estimates for absorption rate constant, volume of distribution and clearance were 0.895 h(-1) , 5340 l and 130 l h(-1) , respectively. The calculated half-life of sertraline following overdose was 28 h (IQR 19.4-30.6h). When given up to 4 h post-overdose, SDAC significantly increased the clearance of sertraline by a factor of 1.9, decreased the area under the curve and decreased the maximum plasma concentration (Cmax ). CONCLUSIONS:Sertraline had linear kinetics in overdose with parameter values similar to those in therapeutic use. SDAC is effective in increasing clearance when given 1.5 to 4 h post-overdose.
Authors: J H Kristensen; K F Ilett; L J Dusci; L P Hackett; P Yapp; R E Wojnar-Horton; M J Roberts; M Paech Journal: Br J Clin Pharmacol Date: 1998-05 Impact factor: 4.335
Authors: Angela L Chiew; Daniel F B Wright; Nicola M Dobos; Kylie McArdle; Ahmed A Mostafa; Annemarie Newth; Michael S Roberts; Geoffrey K Isbister Journal: Br J Clin Pharmacol Date: 2018-04-17 Impact factor: 4.335
Authors: Ali A Alhadab; Joshua Rhein; Lillian Tugume; Abdu Musubire; Darlisha A Williams; Mahsa Abassi; Melanie R Nicol; David B Meya; David R Boulware; Richard C Brundage Journal: J Pharmacokinet Pharmacodyn Date: 2019-10-04 Impact factor: 2.745
Authors: Geoffrey K Isbister; Kalana Maduwage; Ana Saiao; Nicholas A Buckley; Shaluka F Jayamanne; Shahmy Seyed; Fahim Mohamed; Umesh Chathuranga; Alexandre Mendes; Chandana Abeysinghe; Harindra Karunathilake; Indika Gawarammana; David G Lalloo; H Janaka de Silva Journal: PLoS Negl Trop Dis Date: 2015-07-02
Authors: Mohamad Shebley; Akshanth R Polepally; Ahmed Nader; Juki W Ng; Insa Winzenborg; Cheri E Klein; Peter Noertersheuser; Megan A Gibbs; Nael M Mostafa Journal: Clin Pharmacokinet Date: 2020-03 Impact factor: 6.447
Authors: Akshanth R Polepally; Juki W Ng; Ahmed Hamed Salem; Matthew B Dufek; Apurvasena Parikh; David C Carter; Kent Kamradt; Nael M Mostafa; Mohamad Shebley Journal: J Clin Pharmacol Date: 2020-07-07 Impact factor: 3.126