Disposition Kinetics of Caffeine and Paraxanthine in Nile Tilapia (Oreochromis niloticus): Characterization of the Main Metabolites

Abstract

The reproductive and developmental toxicities of caffeine (CA) reported in mammals have been linked with the characteristics of its kinetic disposition. Because undesirable reproductive effects in fish have also been reported, and considering that CA has been found worldwide at relatively high concentrations in most bodies of waters, this study evaluated the disposition kinetics of CA and its main metabolite paraxanthine (1,7-dimethylxanthine; PX) in Nile tilapia after a single intraperitoneal administration (4 mg/kg). CA showed rapid absorption, first-order elimination with biexponential decay, rapid intercompartmental transfer, wide distribution in almost the entire body water (apparent volume of distribution [Vd(ss)] 0.45 l/kg), terminal elimination half-life (t(1/2) (β)) 4.08 h, and systemic clearance (Cl) 0.75 ml/min/kg; there were no important differences between parameters determined in plasma or in other organs (liver and gills). PX was rapidly formed in liver, showing saturable-kinetic properties in this organ, with V(max) 8.11 μg/g h and K(m) 12.58 μg/g. The terminal elimination linear process was similar between matrices, with a half-life (t(1/2 el)) 2.12 h, Vd(ss) 0.35 l/kg, and Cl 1.24 ml/min/kg. CA in tilapia was extensively metabolized to 1-methyl-uric acid and 1-methyl-xanthine in all of the organs studied. Metabolic and kinetic patterns were comparable with those reported for mammals. The observation of a concentration-dependent kinetic of PX is an important finding. Thus, toxicities of CA in fish would appear to be similar to those in mammals and should be considered in the risk assessments for this species, especially during the early stages of development.

Uptake and depuration of pharmaceuticals in reclaimed water by mosquito fish (Gambusia holbrooki): A worst‐case, multiple‐exposure scenario

“…The uptake of caffeine by mosquito fish was very rapid as the internal concentration reached a plateau and remained approximately constant after 5 h of exposure. Similar uptake behavior was also documented in Nile tilapia (Oreochromis niloticus) [17]. However, the depuration rate of caffeine in mosquito fish was much slower than that found in Nile tilapia, in which caffeine had a half-life of 4.95 h [17], compared with the 141-h half-life for mosquito fish calculated in the present study.…”

“…Similar uptake behavior was also documented in Nile tilapia (Oreochromis niloticus) [17]. However, the depuration rate of caffeine in mosquito fish was much slower than that found in Nile tilapia, in which caffeine had a half-life of 4.95 h [17], compared with the 141-h half-life for mosquito fish calculated in the present study. The results indicate that caffeine would be taken up by mosquito fish and Nile tilapia at relatively the same rate but would remain in mosquito fish for a longer time and, therefore, pose higher risks than it does to Nile tilapia.…”

Effects of triclocarban, N,N‐diethyl‐meta‐toluamide, and a mixture of pharmaceuticals and personal care products on fathead minnows (Pimephales promelas)

“…Some of the most commonly detected PPCPs are the bactericides triclocarban and triclosan, the insect repellent N,N-diethyl-metatoluamide (DEET), the nonsteroidal anti-inflammatory drugs naproxen and ibuprofen, and caffeine. Water concentrations range in the parts per trillion to low parts per billion from 0.1 mg/L to 2.0 mg/L [8][9][10][11][12][13][14].…”