Disposition kinetics of caffeine and paraxanthine in Nile tilapia (Oreochromis niloticus): characterization of the main metabolites.
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.
Gómez-Martínez
Lisbeth E
LE
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Departamento de Recursos del Mar, Unidad Mérida, Km 6 Antigua Carretera a Progreso, 97310 Mérida, Yucatán, Mexico. lgomez@mda.cinvestav.mx
D000818:Animals; D002110:Caffeine / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D023681:Cichlids / Q000097:blood / Q000378:metabolism*; D008297:Male; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014874:Water Pollutants, Chemical / Q000493:pharmacokinetics*
D014874:Water Pollutants, Chemical; D002110:Caffeine; D013806:Theophylline; C021183:1,7-dimethylxanthine