The influence of drug polarity on the absorption of opioid drugs into CSF and subsequent cephalad migration following lumbar epidural administration: application to morphine and pethidine.
This study examines the influence of drug polarity on the rate and extent of drug absorption into cerebrospinal fluid (CSF) following lumbar epidural administration. Twelve patients with pain secondary to cancer were simultaneously administered both morphine (10 mg) and pethidine (50 mg) in 10 ml of normal saline via an epidural catheter inserted in the lumbar region (usually L2,3) and attached to a subcutaneously implanted portal reservoir. Frequent blood samples were collected to characterise the vascular uptake of both opioids. In addition, a single CSF sample was collected in each patient from the C7-T1 interspace at one of the following times: 10, 30, 60, 120, 180 and 240 min. There was a rapid vascular uptake of morphine from the epidural space with a mean (+/- S.D.) peak concentration of 173 +/- 80 ng/ml (range 52-345 ng/ml) and a time-to-peak concentration of 8 +/- 6 min (range 2-17 min). In contrast, the vascular uptake of pethidine was more variable with a mean (+/- S.D.) concentration of 274 +/- 294 ng/ml (range 80-1113 ng/ml) and the time-to-peak concentration was 21 +/- 26 min (range 2-75 min). There was a rapid absorption of pethidine across the dura mater into the CSF with peak CSF concentrations between 1400 and 1650 ng/ml occurring between 10 and 60 min in samples collected cephalad (C7-T1 interspace) from the administration point in the lumbar region. However, the peak morphine concentration in CSF was delayed relative to the pethidine peak and occurred at 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Pain Management Unit, Department of Anaesthesia and Intensive Care, Flinders Medical Centre, Bedford Park, S.A. 5042 Australia.
Geoffrey K
GK
Gourlay
David A
DA
Cherry
John L
JL
Plummer
Peter J
PJ
Armstrong
Michael J
MJ
Cousins
D001812:Blood-Brain Barrier; D055598:Chemical Phenomena; D002621:Chemistry; D004359:Drug Therapy, Combination; D006801:Humans; D007268:Injections, Epidural; D008614:Meperidine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009369:Neoplasms / Q000503:physiopathology*; D010146:Pain / Q000134:cerebrospinal fluid / Q000188:drug therapy*
D009020:Morphine; D008614:Meperidine