Abstract
The transport mechanisms of beta-lactam antibiotics in the rat kidney and liver were studied with an in vivo tissue-sampling single-injection technique using [3H]benzylpenicillin [( 3H]PCG) as a substrate. Concentration-dependent uptake of [3H]PCG was observed in the kidney, and the in vivo kinetic parameters were estimated as follows: the maximum uptake rate (Jmax) was 6.88 mumol/min/g of kidney, MIchaelis constant (Kt) was 1.39 mM and nonsaturable first-order rate constant (kd) was 0.414 ml/min/g of kidney. The uptake of [3H]PCG was inhibited by organic anions but not by organic cations. Several beta-lactam antibiotics also reduced the uptake of [3H]PCG. Furthermore, the organic anion, probenecid, and beta-lactam antibiotic, cefpiramide, showed a dose-dependent inhibitory effect. These results suggest participation of an organic anion transport system in uptake of beta-lactam antibiotics across the renal plasma membrane. Saturable uptake of [3H]PCG was also observed in the liver and Jmax, Kt and Kd were estimated to be 3.62 mumol/min/g of liver, 3.59 mM and 0.223 ml/min/g of liver, respectively. The in vivo influx rate calculated from Jmax/Kt in the liver was 1.01 ml/min/g of liver and was close to the in vitro value, 1.54 ml/min/g of liver, estimated previously from isolated hepatocytes. Although dipeptides and organic cations showed no effect on the hepatic uptake of [3H]PCG, probenecid significantly reduced its uptake. Several beta-lactam antibiotics also reduced the uptake of [3H]PCG by the liver. These features of the hepatic uptake of beta-lactam antibiotics through an organic anion transport system are in agreement with the previous results obtained in isolated hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Log in using your username and password
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.