Abstract | AIMS: METHODS: Eleven healthy subjects participated in a double-blind, randomized, placebo-controlled, four-way cross-over study comparing the effects of single doses of placebo and slow-release dihydrocodeine 60 mg with and without premedication with quinidine sulphate 50 mg on electrical, heat and rectal distension pain tolerance thresholds. Plasma concentrations and urinary excretion of dihydrocodeine and dihydromorphine were measured. RESULTS: In quinidine-induced poor metabolizers the plasma concentrations of dihydromorphine were reduced between 3 and 4 fold from 1.5 h to 13.5 h after dosing (P < 0.005) and urinary excretion of dihydromorphine in the first 12 h was decreased from 0.91% to 0.28% of the dihydrocodeine dose (P < 0.001). Dihydrocodeine significantly raised the heat pain tolerance thresholds (at 3.3 h and 5 h postdosing, P < 0.05) and the rectal distension defaecatory urge (at 3.3 h and 10 h postdosing, P < 0.02) and pain tolerance thresholds (at 3.3 h and 5 h postdosing, P < 0.05) compared with placebo. Premedication with quinidine did not change the effects of dihydrocodeine on pain thresholds, but decreased the effect of dihydrocodeine on defaecatory urge thresholds (at 1.5 h, 3.3 h and 10 h postdosing, P < 0.05). CONCLUSIONS:
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Authors | C H Wilder-Smith, E Hufschmid, W Thormann |
Journal | British journal of clinical pharmacology
(Br J Clin Pharmacol)
Vol. 45
Issue 6
Pg. 575-81
(Jun 1998)
ISSN: 0306-5251 [Print] England |
PMID | 9663813
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics, Opioid
- Dihydromorphine
- Quinidine
- dihydrocodeine
- Codeine
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Topics |
- Adult
- Analgesics, Opioid
(metabolism, pharmacokinetics, pharmacology)
- Codeine
(analogs & derivatives, metabolism, pharmacokinetics, pharmacology)
- Cross-Over Studies
- Dihydromorphine
(metabolism, pharmacokinetics, pharmacology)
- Double-Blind Method
- Electric Stimulation
- Humans
- Male
- Pain Measurement
- Pain Threshold
(drug effects)
- Quinidine
(pharmacology)
- Skin Physiological Phenomena
(drug effects)
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