Transfer of Timentin (ticarcillin and clavulanic acid) across the in vitro perfused human placenta: comparison with other agents.

Abstract

In vitro perfusion of human placentas was used to quantify the net placental transfer of ticarcillin and clavulanic acid. Placentas were obtained from uncomplicated pregnancies at term. The maternal and fetal circulations were reestablished at flow rates of 17.5 ml/min and 5 ml/min, respectively. Open circulations were used to evaluate steady-state pharmacodynamics and transplacental gradient formation. Drug levels were measured by high-pressure liquid chromatography. The clearance index of ticarcillin was 0.037 +/- 0.004. The fetal/maternal ratio was 0.91. Therapeutic concentrations of clavulanate (2 to 6 micrograms/ml) in the maternal media resulted in undetectable transfer to the fetal compartment. By using higher levels of clavulanate, a clearance index of 0.061 +/- 0.001 (mean +/- SEM) and 1:1 fetal/maternal gradient was obtained. These data correspond to relatively low transfer of ticarcillin with a cord/maternal ratio of < 1. Clavulanate transfer is slightly greater. Agents with similar activity and superior transfer would optimize intrauterine treatment.