title: CSF and plasma pharmacokinetics of pethidine and norpethidine in man after epidural and intrathecal administration of pethidine.
abstract: The disposition of pethidine and its main metabolite, norpethidine, in cerebrospinal fluid (CSF) and plasma was studied in 11 thoracic surgery patients after lumbar epidural (100 mg; n = 6) or lumbar intrathecal (25 mg; n = 5) administration of pethidine. Pethidine appeared more slowly in plasma after intrathecal than after epidural administration (tmax 2.3 h and 14 min, respectively), but systemic bioavailability was similar. The CSF concentrations of pethidine were higher than those in plasma after both routes of administration. The maximal CSF/plasma concentration ratio was 6000 to 45,000 after intrathecal administration but was only 26 to 97 after the epidural route. Pethidine was rapidly distributed in CSF; nine to ten h after the intrathecal and epidural injections the CSF/plasma concentration ratios were 12 to 89 and 2 to 33, respectively. The calculated bioavailability in CSF of epidural pethidine was 10.3%. The terminal elimination half-life of pethidine was 6.0 h (CSF) and 5.4 h (plasma) after intrathecal administration and 8.6 h (CSF) and 8.8 h (plasma) after epidural injection. The volume of distribution of unchanged pethidine in the subarachnoid space was 13 ml.kg-1 and clearance from the CSF was 15 microliters.kg-1.min-1. In all patients receiving intrathecal pethidine and in some patients after epidural pethidine, CSF norpethidine concentrations were higher than those in plasma; the maximum CSF norpethidine was 102 to 1211 ng.ml-1 and 14 to 210 ng.ml-1 and the maximum CSF/plasma norpethidine concentration ratios were 21 to 652 and 0.6 to 14 times after intrathecal and epidural administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Anaesthesia and Intensive Care, Sahlgrenska Hospital, Gothenburg, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Nordberg
authors.forename: V
authors.initials: V
authors.lastname: Hansdottir
authors.forename: U
authors.initials: U
authors.lastname: Bondesson
authors.forename: L O
authors.initials: LO
authors.lastname: Boréus
authors.forename: T
authors.initials: T
authors.lastname: Mellstrand
authors.forename: T
authors.initials: T
authors.lastname: Hedner
mesh_terms: D005260:Female; D006801:Humans; D007268:Injections, Epidural; D007278:Injections, Spinal; D008297:Male; D008614:Meperidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*
chemical_list: D008614:Meperidine; C002752:normeperidine