CSF morphine levels after lumbar intrathecal administration of isobaric and hyperbaric solutions for cancer pain.
The objectives of this study were to compare the pharmacokinetic properties and the duration of analgesia following intrathecal administration (L5-S1) of 2 mg morphine in 2 forms: (1) an isobaric (NaCl 0.9%) and (2) a hyperbaric solution (7% dextrose). The study was carried out on 5 cancer patients with severe, intractable pain in the lower half of the body. Samples of CSF were collected at the level of the 10th thoracic vertebra at regular intervals for 15 h after administration. Morphine concentrations were determined by HPLC. The pharmacokinetic properties of the solutions (I and II) were quite different. Peak levels (I) were reached in 5-15 min (30 and 60 micrograms/ml); they then fell rapidly during the 1st hour (7 and 11 micrograms/ml) with an elimination half-life of 10 and 15 min, followed by a change in slope (elimination half-life of 108 and 140 min). Peak levels (II) were reached in 4-5 h (0.8-3.3 micrograms/ml); they then fell progressively according to a single exponential function (elimination half-life: 144-246 min). The duration of analgesia for a dose of 2 mg was 30 h for solution 2 and 24 h for solution 1. The hyperbaric solution, which produced the same degree of analgesia as the isobaric solution, limited the cephalad diffusion of morphine and reduced or abolished the central depressant effects of the drug.
Caute
B
B
Laboratoire de Pharmacie Galénique, Faculté des Sciences Pharmaceutiques, Université Paul Sabotier, 31400 ToulouseFrance Laboratoire de Pharmacologie et de Toxicologie Fondamentales, CNRS, 31077 Toulouse Cedex France Laboratoire de Neurochirurgie et Neurobiologie Appliquée, Clinique Universitaire de Neurochirurgie, CHU Toulouse-Rangueil, Université Paul Sabatier, 31400 ToulouseFrance.
Monsarrat
B
B
Gouardères
C
C
Verdie
J C
JC
Lazorthes
Y
Y
Cros
J
J
Bastide
R
R
D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008159:Lumbar Vertebrae; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009369:Neoplasms / Q000503:physiopathology*; D010148:Intractable Pain / Q000188:drug therapy* / Q000503:physiopathology; D012996:Solutions; D013046:Specific Gravity
D012996:Solutions; D009020:Morphine