PHARMACOKINETIC PROFILE OF MORPHINE IN PARTURIENTS FOLLOWING INTRAVENOUS OR EPIDURAL ADMINISTRATION

Background and Objectives. Study of the pharmacokinetic profile of mor phine following intravenous or epidural administration in parturients undergoing elective cesarean delivery. Methods. Sixteen healthy partur ients scheduled for elective cesarean delivery received lumbar epidura l anesthesia to a T4 sensory level using lidocaine 2% with epinephrine 1:200,000. One hour after the last local anesthetic dose was given, p atients were randomized to receive morphine 5 mg either intravenously (n = 8) or epidurally (n = 8). Venous blood samples were obtained at t imes 0, 0.033, 0.067, 0.1, 0.184, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 ho urs and urine specimens starting at 0.25 hour. Plasma and urine unconj ugated and conjugated morphine levels were measured using radioimmunoa ssay. Results. After 15 minutes the plasma unconjugated morphine level was similar in the intravenous and epidural groups. Mean plasma conce ntration of unconjugated morphine at 0.033, 0.067, 0.1, and 0.184 hour in the intravenous group exceeded the corresponding values in the epi dural group (P < .05, t-test) with no significant differences at other time periods. Maximum plasma concentration of unconjugated morphine o ccurred 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 conjugate s appeared quickly in both groups, with the maximum concentration occu rring at 1 hour (38 +/- 11 ng/mL; range, 9.3-65) in the intravenous gr oup and at 2 hours (26.4 +/- 3 ng/mL; range, 13-29) in the epidural gr oup. The plasma concentration decay curves followed a triexponential p attern in the intravenous group. In the epidural group a distinct abso rption phase was seen, followed by a biexponential decay. No significa nt difference was seen in AUC, AUMC, Cl, Vss, MRT, or t1/2beta between the two routes of administration. Urinary morphine concentration and total 24 hours excretion of unconjugated and total morphine were highe r in the intravenous group. Conclusions. Compared to epidural administ ration, intravenous administration produces higher plasma morphine val ues in the first 15 minutes and greater urinary excretion of morphine with no significant difference in the subsequent disposition in the bo dy.