The transport mechanisms of β-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 (J(max)) was 6.88 μmol/min/g of kidney, Michaelis constant (K(t)) was 1.39 mM and nonsaturable first-order rate constant (k(d)) was 0.414 ml/min/g of kidney. The uptake of [3H]PCG was inhibited by organic anions but not by organic cations. Several β-lactam antibiotics also reduced the uptake of [3H]PCG. Furthermore, the organic anion, probenecid, and β-lactam antibiotic, cefpiramide, showed a dose-dependent inhibitory effect. These results suggest participation of an organic anion transport system in uptake of β-lactam antibiotics across the renal plasma membrane. Saturable uptake of [3H]PCG was also observed in the liver and J(max), K(t) and K(d) were estimated to be 3.62 μmol/min/g of liver, 3.59 mM and 0.223 ml/min/g of liver, respectively. The in vivo influx rate calculated from J(max)/K(t) 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 β-lactam antibiotics also reduced the uptake of [3H]PCG by the liver. These features of the hepatic uptake of β-lactam antibiotics through an organic anion transport system are in agreement with the previous results obtained in isolated hepatocytes. Thus, it is confirmed that the transport system available for β-lactam antibiotics observed in isolated hepatocytes reflects the in vivo transport into the liver.
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 1990 Jan 1|
ASJC Scopus subject areas
- Molecular Medicine