Secretion of Dilevalol in Breast Milk

The pharmacokinetics of unchanged and total (unchanged plus Glusulase [Biotechnology Systems, Boston, MA]) released dilevalol and secretion into human breast milk was studied in six healthy breast‐feeding female volunteers administered a single 400‐mg dilevalol hydrochloride capsule. In plasma, the mean C max for unchanged dilevalol, 485 ng/mL was reached at 0.8 hour (t max ) and the AUC(48 hours) was 1435 hr × ng/mL. Pharmacokinetic analysis of unchanged dilevalol in plasma showed that dilevalol was distributed and eliminated with half‐lives of 0.9 and 8.2 hours, respectively. Breast milk concentrations of unchanged dilevalol as a function of time, paralleled those of plasma but were consistently lower. The milk C max , 149 ng/mL, occurred during the 0 to 2 hour collection interval; the AUC(42 hours) for unchanged dilevalol in milk was 663 hr × ng/mL. The mean milk to plasma concentration ratio was 0.46. The unchanged dilevalol plasma concentrations were 12 to 18% those of total drug suggesting that the drug is extensively conjugated. By contrast, the concentrations of unchanged dilevalol in breast milk, based on C max and AUC data were 63 to 94% those of total drug, indicating that very little conjugated drug is secreted into breast milk. Through 48 hours, a mean of only 27 μg dilevalol or 0.007% of the administered dose was secreted into breast milk, which is much less than that reported for other beta blockers.