Placental transfer of thiamphenicol in the rat.

Measurement of thiamphenicol transfer to the rat embryo during organogenesis was performed as one step of the determination of possible drug embryotoxicity in man. Extrapolation of data on animal embryotoxicity to man will only become possible when data on the toxicokinetic properties of the substance under investigation are available for both animal and man. 1) Thiamphenicol, given between day 11.5 and 14 of rat gestation, rapidly reached the embryo; 4--6 h after single i.v. or s.c. injection, embryonic and maternal thiamphenicol levels became equal and decreased from that time on at the same rate. 2) No evidence was found for development of a placenta barrier with increasing placental function. The same dose applied at different developmental stages yielded the same embryonic drug concentrations. 3) Elimination via kidney (unchanged) or bile (glucuronide), may become rate-limiting for thiamphenicol excretion. Doses exceeding 50 mg/kg (i.v.) or approx. 100 mg/kg (s.c.) yielded thiamphenicol levels higher than those expected from linear dose-concentration relationships. 4) Drug concentrations (greater than 3--5 micrograms/g wet weight) obtained with dosing regimens (greater than 100 mg/kg/day) used for experimental induction of embryolethality in rats are equal to those necessary for inhibition of mitochondrial protein synthesis in vitro and to those necessary for treatment of bacterial infections in man.