Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jan 2001
Randomized Controlled Trial Clinical TrialADL 8-2698, a trans-3,4-dimethyl-4-(3-hydroxyphenyl) piperidine, prevents gastrointestinal effects of intravenous morphine without affecting analgesia.
ADL-8-2698 is a novel peripherally restricted opioid antagonist that may selectively prevent opioid-induced gastrointestinal effects without reversing analgesia. Gastrointestinal transit time (lactulose hydrogen breath test) was measured in 14 volunteers with oral and intravenous placebo, oral placebo and intravenous morphine (0.05 mg x kg(-1)), and oral ADL 8-2698 (4 mg) and intravenous morphine (0.05 mg x kg(-1)) in a double blind, cross-over study. Morphine prolonged gastrointestinal transit time from 69 to 103 minutes (P = .005); this was prevented by ADL 8-2698 (P = .004). ⋯ Analgesia and pupil constriction were measured. Morphine analgesia and pupil constriction were unaffected by ADL 8-2698 and differed from placebo (P < .002). We conclude that ADL 8-2698 prevents morphine-induced increases in gastrointestinal transit time by means of selective peripheral opioid anitagonism without affecting central opioid analgesia.
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Clin. Pharmacol. Ther. · Dec 2000
Randomized Controlled Trial Comparative Study Clinical TrialRandomized placebo-controlled trial of the activity of the morphine glucuronides.
Morphine-6-glucuronide (M6G) is an active metabolite of morphine with potent analgesic activity. Morphine-3-glucuronide (M3G), the most prevalent metabolite, has minimal affinity for opioid receptors. It has been suggested from animal model data and by examination of metabolite ratios in humans that M3G may functionally antagonize the respiratory depressant and analgesic actions of morphine and M6G. ⋯ M3G appears to be devoid of significant activity; in these circumstances and at these doses, it does not antagonize either the analgesic or respiratory depressant effects of M6G or morphine.
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Clin. Pharmacol. Ther. · Nov 2000
Randomized Controlled Trial Clinical TrialMyocardial efficiency during levosimendan infusion in congestive heart failure.
Levosimendan, a novel calcium-dependent calcium sensitizer of the myocardial contractile proteins, also enhances diastolic relaxation and induces peripheral vasodilation by opening potassium channels. To assess the combined energetical effects of levosimendan infusion in vivo, we performed positron emission tomography in patients with decompensated chronic heart failure. ⋯ Levosimendan has an energetically favorable short-term profile in the treatment of congestive heart failure. It enhances cardiac output without oxygen wasting, particularly by improving efficiency in the right ventricle.
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Clin. Pharmacol. Ther. · Nov 2000
Randomized Controlled Trial Clinical TrialThe cytochrome P450 3A4 inhibitor itraconazole markedly increases the plasma concentrations of dexamethasone and enhances its adrenal-suppressant effect.
To examine the possible interaction of itraconazole with orally and intravenously administered dexamethasone. ⋯ Itraconazole markedly increases the systemic exposure to and effects of dexamethasone. A careful follow-up is recommended when itraconazole or other potent inhibitors of the cytochrome P450 3A4 are added to the drug regimen of patients receiving dexamethasone.
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Clin. Pharmacol. Ther. · Sep 2000
Randomized Controlled Trial Multicenter Study Clinical TrialIbuprofen plus caffeine in the treatment of tension-type headache.
The effectiveness of caffeine as an adjuvant to ibuprofen has been documented in investigations of acute pain. Our objectives were to assess this agent in the treatment of tension-type headache and to establish clinical trial methods capable of assessing this agent in comparison with various tension headache treatments. Stopwatch technology was used for measurement techniques. ⋯ Sensitive methods have been introduced to assess differences in analgesia among over-the-counter analgesic agents in relieving tension-type headache pain. A double-blind study with this method suggests that ibuprofen and caffeine administered together provides greater analgesic effectiveness than either component alone.