A revised excretion factor for estimating ketamine consumption by wastewater-based epidemiology – Utilising wastewater and seizure data

•An extensive review to revise the excretion factors for ketamine and norketamine.•Currently used excretion factors of ketamine and norketamine were probably not appropriate.•It is practical to use ketamine as biomarker for estimating ketamine consumption by WBE.•A revised excretion factor of 20% is recommended for ketamine consumption estimation.•WBE data are useful for refining excretion factors when pharmacokinetic data are limited. The rate of drug excretion (excretion factor) is a critical parameter for monitoring drug consumption in the population by wastewater-based epidemiology (WBE). Previous studies have refined excretion factors for common illicit drugs, such as cocaine, amphetamine, methamphetamine, heroin, to improve the accuracy and reduce uncertainty in back-calculating consumption. Nevertheless, for ketamine, one of the most prevalent psychoactive substances, a careful review of its excretion factors has not been performed due to limited pharmacokinetic data. Here we review WBE studies and seizure data to refine and validate the excretion factors for ketamine and norketamine. The average ketamine/norketamine ratio in wastewater (5.36) was much higher than that found in urine (0.64), which means that the excretion factors derived only from pharmacokinetics data are not appropriate. Based on the comparison of the ratio between estimated consumptions of ketamine and methamphetamine by WBE with their corresponding ratio in official seizure data, a revised WBE excretion factor of 20% was proposed for ketamine following this review and applied to estimate the ketamine consumption in China. The revised estimates of ketamine consumption corresponded well with drug statistics. This suggests that the revised ketamine excretion factor is appropriate for estimating ketamine consumption by WBE. Systematic review of WBE studies is a suitable approach to refine the excretion factors for substances with inadequate pharmacokinetic data.