TERFENADINE PHARMACOKINETICS IN BREAST-MILK IN LACTATING WOMEN

The excretion of terfenadine into breast milk has not been reported previously. Disposition of terfenadine was prospectively studied in four healthy lactating mothers (age, 33 +/- 4 years). Subjects received 60 mg terfenadine every 12 hours over a period of 48 hours to achieve steady-state milk and plasma concentrations. Milk and plasma samples were collected at 1/2, 1, 1 1/2, 2, 3, 4, 6, 8, 12, 24, and 30 hours after the last dose. Terfenadine and its active metabolite milk and plasma concentrations were quantitated by HPLC. Terfenadine was not detected in milk or plasma. Mean +/- SD active metabolite data for milk and plasma are as follows: C-max (ng/ml), 41.0 +/- 16.4 for milk, 309.0 +/- 120.5 for plasma; t(max) (hours), 4.3 +/- 2.4 for milk, 3.9 +/- 3.0 for plasma; t1/2 beta (hours), 14.2 +/- 5.4 for milk, 11.7 +/- 6.4 for plasma; AUC(0-12) (ng . hr/ml) 320.4 +/- 99.8 for milk, 1590.0 +/- 300.4 for plasma. Metabolite milk/plasma(AUC(0-12)) ratios ranged from 0.12 to 0.28 (mean, 0.21 +/- 0.07). Newborn dosage estimates based on the highest measured concentration of terfenadine metabolite in milk suggests the maximum level of newborn exposure would not exceed 0.45% of the recommended maternal weight-corrected dose. Estimated amounts consumed by the neonate after the mother is given the recommended dose of the drug are not likely to result in plasma levels producing untoward effects.