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Pharmacology (82)
Author(s) -
Eckhardt Klaus,
Ammon Susanne,
Hofmann Ute,
Riebe Anja,
Gugeler Nadja,
Mikus Gerd
Publication year - 2001
Publication title -
pain practice
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 58
eISSN - 1533-2500
pISSN - 1530-7085
DOI - 10.1111/j.1533-2500.2001.1011-82.x
Subject(s) - placebo , morphine , medicine , analgesic , pharmacokinetics , anesthesia , gabapentin , pharmacodynamics , adverse effect , pharmacology , alternative medicine , pathology
Gabapentin enhances the analgesic effect of morphine in healthy volunteers. (Dr. Margarete Fischer Bosch Institut fuer Klinische Pharmakologie, Stuttgart, Germany) Anesth Analg 2000;91:185–191. This randomized, placebo‐controlled, double‐blinded study investigated the pharmacodynamic and pharmacokinetic interaction of Gabapentin (GBP) and morphine in 12 healthy male volunteers. Morphine (60 mg, controlled release) or placebo was administered at 8:00 a.m., and GBP (600 mg) or placebo was administered at 10:00 a.m., thus comparing the analgesic effect of placebo + GBP (600 mg) with placebo + placebo and morphine (60 mg) + GBP in comparison to morphine plus placebo by using the cold pressor test. The duration and intensity of the side effects were assessed by using visual analog scales. The analgesic effect was evaluated by the change in the area under the curve of pain tolerance. Placebo + GBP did not present any significant analgesic effect compared with placebo + placebo. A siginificant increase in pain tolerance was observed comparing the combination of morphine and GBP with morphine and placebo. The observed adverse events after placebo + GBP were not significantly different compared with placebo + placebo. Morphine + placebo led to the expected opioid‐mediated side effects. They were significantly more pronounced compared with placebo + placebo, but did not differ significantly compared with the combination of morphine + GBP. Concerning the pharmacokinetic variables of morphine and its glucuronides, no significant difference between morphine + placebo and morphine + GBP was observed, whereas the area under the curve of GBP significantly increased, and apparent oral clearance and apparent renal clearance of GBP decreased when morphine was administered concomitantly. These results suggest 2 different sites for the pharmacokinetic interaction—1 at the level of absoption and the other at the level of elimination. The study reveals both a pharmacodynamic and pharmacokinetic interaction between morphine and GBP, leading to an increased analgesic effect of morphine + GBP. These results and the good tolerability of GBP should favor clinical trials investigating the clinical relevance of the combination of morphine and GBP for treating severe pain.