Abstract
AimsTo investigate the pharmacokinetics (PK) of sertraline in overdose and the effect of single dose activated charcoal (SDAC).
MethodsPatients presenting to a toxicology unit with sertraline overdoses had demographic and clinical information recorded, and serial serum collected for measurement of sertraline concentrations. Monolix (R) 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.
ResultsThere were 77 timed sertraline concentrations measured in 28 patients with sertraline overdoses with a median dose of 1550mg (250-5000mg). SDAC was given to seven patients between 1.5 and 4h post-overdose. A one compartment model with lag time of 1h 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 0.895h(-1), 5340l and 130lh(-1), respectively. The calculated half-life of sertraline following overdose was 28h (IQR 19.4-30.6h). When given up to 4h 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 (C-max).
ConclusionsSertraline 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 4h post-overdose.