Pharmacokinetic profile of epidural meperidine with and without dextran 70 To evaluate the effect of dextran 70 on the kinetics of epidural meperidine, 10 female patients anesthetized with nitrous oxide and halothane were studied. Meperidine, 1 mg kg- was administered epidurally in either 10 ml dextran 70 in saline solution (group I) or 10 ml saline solution (group II, control subjects). Plasma concentration of meperidine was determined for 10 hours after its administration with GC. Meperidine plasma concentration-time curves could be best resolved into three exponential terms with a lag time in both groups of patients. The disposition kinetics were described adequately by a three- compartment model. This study demonstrated that apart from a significantly longer lag time and smaller k10 (apparent first-order rate constant for elimination of meperidine from the central compartment), the addition of dextran did not alter significantly the kinetic parameters of epidural meperidine. (CLINT PHARMACOL THER 1988;43:407-11.) Mohamed Naguib, M.B., B.Ch., M.Sc., F.F.A.R.C.S.I., Hesharn Farag, M.B., B.Ch., F.F.A.R.C.S., Afaf Absood, B.S., M.S., Abdulaziz Al Khawaja, Ph.D., and Gamil H. Absood, Ph.D. Al Khobar, Saudi Arabia Since the initial positive report by Behar et al.' in 1979, epidural administration of opioids for postoper- ative analgesia has gained widespread popularity. How- ever, it was noted that the duration of analgesia pro- duced by different opioids was variable,' being shortest with lipophilic drugs.3-5 By virtue of its lipophilicity, meperidine was found to be removed rapidly from the spinal cord.' Of the opioids, the phenylperidine derivatives such as meperidine have the structure closest to that of the local anesthetics, with similar physicochemical prop- erties.' For instance meperidine has a molecular weight of 247 and a pKa of 8.5, whereas lidocaine has a mo- lecular weight of 234 and a pKa of 7.9. This could account for the similarity in the absorption half-life of the epidurally administered meperidine and lidocaine.' Unlike local anesthetics, addition of epinephrine to the epidurally administered meperidine enhances nei- ther quality nor duration of analgesia.' However, it has been shown by several investigators' that addition of dextran to local anesthetic solutions prolongs the an- esthetic effect. This study was designed to investigate the influence From the Departments of Anaesthesiology, Clinical Pharmacology, and Biostatistics, King Faisal University, King Fand Hospital. Received for publication April 13, 1987; accepted Aug. 20, 1987. Reprint requests: Dr. Mohamed Naguib, King Faisal University, King Fand Hospital, PO Box 2208, Al Khobar, 31952, Saudi Arabia. of dextran 70 on the pharmacokinetics of epidural me- peridine. METHODS Ten female patients of American Society of Anes- thesiologist Classification physical status I or II, un- dergoing gallbladder surgery with subcostal incision, were studied. The mean age and body weight ( ± SD) of the patients were 40.2 5.5 years and 67.9 -± 8 kg, respectively. The protocol was approved by the hospital review committee and informed consent was obtained. All patients were premedicated with 10 to 15 mg diazepam orally 90 minutes before surgery. No patient received narcotic premedication. In the operating room an intravenous line was estab- lished, the ECG was monitored continuously, and ar- terial blood pressure was monitored every 5 minutes with an electronic oscillotonometer. Anesthesia was induced with thiopental, 5 mg/kg, and, after intubation, with pancuronium, 0.1 mg/kg, maintained by 70% nitrous oxide in oxygen and 0.5% to 1% halothane. Ventilation was controlled with a Manley Servovent (Medishield, U.K.) to maintain normocapnia and end-tidal CO2 was monitored by a Datex infrared CO2 analyzer (NORMOCAP). The epidural catheters were inserted after induction of anesthesia under aseptic technique at the lumbar ver- tebral level of L1-2 and advanced cephalad for a few centimeters. Patients were allocated randomly into two 407