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A two‐dose epidural morphine regimen in cesarean section patients: pharmacokinetic profile

The maternal pharmacokinetics, metabolism of, and possible neonatal transmission of epidural morphine in cesarean section patients were investigated. Maternal plasma, breast milk, and maternal and neonatal urine concentrations of unconjugated and conjugated (UM and CM) morphine were measured in patients given two 5‐mg doses of epidural morphine for post‐cesarean section analgesia. The first dose was administered after delivery and the second dose 24 h later. Maternal venous blood samples (n = 10) were collected at times 0, 0.25, 0.5, 1, 2, 3, 4, 6, 12, and 24 h after each dose, and maternal urine was collected for three consecutive 24‐h periods (n = 30). Maternal breast milk (n = 30), and neonatal urine samples (n = 20) were also collected. Serum, urine, and breast milk UM and CM levels were measured using radioimmunoassay. Pharmacokinetic values were calculated using noncompartmental analysis. The results were expressed as mean ± 1 s.e. mean and analyzed using repeated measures analysis of variance and the paired t‐test. Maternal serum UM remained 40–50% higher, and CM 50–100% higher in the first hour following dose 2 than the respective values after dose 1 (P < 0.05). Values for AUC, AUMC, Tl/2, and MRT increased 28%, 83%, 35% and 36%, respectively, with the second dose (P < 0.05), while CI decreased 19% (P < 0.05) with no significant difference in Vss. Total urinary excretion of morphine decreased significantly from 1.98 ± 0.15 mg on day 1 to 1.6 ± 0.2 mg and 0.19 ± 0.002 mg on days 2 and 3, respectively (P < 0.01). Breast milk and neonatal urine contained negligible amounts of morphine, signifying minimal neonatal transfer.