Trimethoprim and sulfamethoxazole transfer in the in vitro perfused human cotyledon.
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Utilizing the in vitro human placental model, we studied the placental transfer of trimethoprim and sulfamethoxazole. At trimethoprim concentrations of 7.2 micrograms/ml, only 1.4 micrograms/ml was transported across the placenta after 1 h, and at concentrations of 1.0 microgram/ml, one half the usual serum level, only 0.08 microgram/ml was transported across the placenta. Maternal concentrations of sulfamethoxazole of 29.6 and 127.7 micrograms/ml resulted in concentrations of 5.1 and 14.8 micrograms/ml on the fetal side, respectively. Thus, it would appear that trimethoprim is slowly transported across the placenta and in low concentrations whereas sulfamethoxazole readily crosses the placenta. The combination of these drugs is useful for treatment of bacteriuria. It may also prove to be especially useful for Pneumocystis carinii infections in pregnant women with AIDS. With a half-life of 13 h for trimethoprim and 6 h for sulfamethoxazole, the drugs are not likely to achieve toxic levels in the fetal compartment. Thus, it would appear that trimethoprim and sulfamethoxazole may be both efficacious and safe for the treatment of both these infections during pregnancy.