Comparison of in vitro drug metabolism by lung, liver, and kidney of several common laboratory species

Abstract

Comparative studies of in vitro drug metabolism by hepatic and extrahepatic tissues have been complicated by the use of a single experimental tissue, few animal species, and variable experimental conditions. In an attempt to minimize these complications, liver, lung and kidney from rat, mouse, rabbit, hamster, and guinea pig were assayed for standard microsomal and soluble fraction enzymes involved in drug biotransformation. For all species, liver was the most active organ. Kidney and lung activities were usually 15%-40% of those found in liver, with kidney slightly more active than lung. No single species demonstrated total superiority in its drug-metabolizing ability, although hamster showed a large number of instances of greatest activity. The rat was a surprisingly poor representative of drug-metabolizing ability; it was superior to the other four species in less than 25% of the instances studied. All species appeared to N-demethylate aminopyrine equally except for high pulmonary and nearly absent renal activities in rabbit and high hepatic activity in hamster. Rat had the lowest level of cytochrome P-450 and low activity of NADPH-cytochrome c reductase. UDP-glucuronyltransferase activity toward the acceptors p-nitrophenol and o-aminophenol was higher in hamster and rabbit than other species. Guinea pig appeared to have the most active soluble fraction enzymes. Mouse lung and kidney had glutathione S-aryltransferase activities 10-fold greater than any other species and comparable to liver activity from rabbit and hamster.