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Development of a "blood-brain barrier" to methadone in the newborn rat.

The chronic administration of dl-methadone to female rats during gestation results in the simultaneous administration of the drug to the unborn fetus. The tissue concentration of methadone in fetal brain is several-fold greater than in maternal brain. Methadone concentration in other maternal tissues studied was higher than in their fetal counterpart. Similar brain concentrations of methadone were seen in 19- to 21-day fetal rats, taken from mothers who had been treated with methadone, as was found in 1-day-old pups which were given an i.p. injection of methadone directly. The amount of methadone concentrating in the brain from a single 5 mg/kg dose increased with increasing postnatal age until about day 15 and then decreased to near adult levels by days 30 to 35. The blood concentration of methadone was more or less constant with all age groups and was significantly lower than brain concentrated at all time periods studied prior to day 30. The data presented would suggest that there is no true blood-brain barrier to methadone in either the young or the adult rat. However, there is some process which limits the brain content of methadone in the adult which is absent in the young animal. This process appears to be developed by about 30 to 35 days after birth. The apparent delay in the developmental processes seen in the pups born to and nursed by mothers chronically treated with methadone is not statistically significant.