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Pharmacokinetic Profile of Morphine in Parturients Following Intravenous or Epidural Administration
  1. Mark I. Zakowski, M.D.,
  2. Sivam Ramanathan, M.D.,
  3. Kenneth M. Sutin, M.D.,
  4. Gilbert J. Grant, M.D. and
  5. Herman Turndorf, M.D.
  1. From the Department of Anesthesiology, New York University Medical Center, New York, New York, and the Department of Anesthesiology and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  1. Reprint requests: Mark Zakowski, M.D., Department of Anesthesiology, New York University Medical Center, 550 First Avenue, New York, NY 10016.


Background and Objectives. Study of the pharmacokinetic profile of morphine following intravenous or epidural administration in parturients undergoing elective cesarean delivery.

Methods. Sixteen healthy parturients scheduled for elective cesarean delivery received lumbar epidural anesthesia to a T4 sensory level using lidocaine 2% with epinephrine 1:200,000. One hour after the last local anesthetic dose was given, patients were randomized to receive morphine 5 mg either intravenously (n = 8) or epidurally (n = 8). Venous blood samples were obtained at times 0, 0.033, 0.067, 0.1, 0.184, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours and urine specimens starting at 0.25 hour. Plasma and urine unconjugated and conjugated morphine levels were measured using radioimmunoassay.

Results. After 15 minutes the plasma unconjugated morphine level was similar in the intravenous and epidural groups. Mean plasma concentration of unconjugated morphine at 0.033, 0.067, 0.1, and 0.184 hour in the intravenous group exceeded the corresponding values in the epidural group (P < .05, t-test) with no significant differences at other time periods. Maximum plasma concentration of unconjugated morphine occurred at or before the first sample at 0.033 hour (126 ± 19 (1SE) ng/mL; range, 71-172) in the intravenous group and at 0.5 hour (14.6 ± 1.2 ng/mL; range, 9.5-22) in the epidural group. Morphine conjugates appeared quickly in both groups, with the maximum concentration occurring at 1 hour (38 ± 11 ng/ mL; range, 9.3-65) in the intravenous group and at 2 hours (26.4 ± 3 ng/mL; range, 13-29) in the epidural group. The plasma concentration decay curves followed a triexponential pattern in the intravenous group. In the epidural group a distinct absorption phase was seen, followed by a biexponential decay. No significant difference was seen in AUC, AUMC, Cl, Vss, MRT, or t1/2β between the two routes of administration. Urinary morphine concentration and total 24 hours excretion of unconjugated and total morphine were higher in the intravenous group.

Conclusions. Compared to epidural administration, intravenous administration produces higher plasma morphine values in the first 15 minutes and greater urinary excretion of morphine with no significant difference in the subsequent disposition in the body.

  • analgesia
  • epidural
  • intravenous
  • morphine
  • pharmacokinetics
  • obstetric

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