Clearance of meperidine and its metabolite normeperidine in hemodialysis patients with chronic noncancer pain.

Abstract

Normeperidine accumulates in patients with impaired renal function and may cause central neurotoxicity. However, some uremic patients still undergo meperidine treatment for chronic pain. To prevent normeperidine side effects and complications, we investigated the clearance rate and extraction ratio of meperidine and normeperidine in hemodialysis patients with chronic pain. Three hemodialysis patients, with diagnoses of chronic pancreatitis, chronic back pain, and intractable intra-abdominal pain, received long-term (more than six months) administration of meperidine for chronic noncancer pain. During regular hemodialysis, 72 blood samples in total were collected from the afferent port, efferent port, and ultradiafiltrate port at eight time points. The plasma concentrations of meperidine and normeperidine were determined by high-performance liquid chromatography. The prehemodialysis plasma concentrations of meperidine and normeperidine were 2963 ± 315 and 2369 ± 1974 ng/mL, which declined to 591 ± 109 and 853 ± 765 ng/mL, with 80% and 65% reduction, respectively. The plasma clearance and extraction ratios of meperidine were 22.7 ± 9.8 mL/minute and 10.1 ± 5.6% and for normeperidine 26.0 ± 11.4 mL/minute and 10.8 ± 2.5%, respectively. Hemodialysis can efficiently remove meperidine and its active metabolite, normeperidine, in uremic patients receiving long-term meperidine therapy for chronic noncancer pain.