Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Oct 2005
Multicenter Study Clinical TrialRosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment.
Systemic exposure to rosuvastatin had been observed to be approximately 2-fold higher in Japanese subjects living in Japan compared with white subjects in Western Europe or the United States. The organic anion transporting polypeptide 1B1 contributes to the hepatic uptake of rosuvastatin. Polymorphisms in the SLCO1B1 gene can lead to reduced transport function in vitro (T 521>C). This study was conducted to determine whether the pharmacokinetic differences between Japanese and white subjects extended to other Asian ethnic groups and to determine whether polymorphisms in the SLCO1B1 gene contribute to any pharmacokinetic differences observed. ⋯ Plasma exposure to rosuvastatin and its metabolites was significantly higher in Chinese, Malay, and Asian-Indian subjects compared with white subjects living in the same environment.
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Clin. Pharmacol. Ther. · Oct 2002
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialPharmacokinetic-pharmacodynamic analysis of drotrecogin alfa (activated) in patients with severe sepsis.
We aimed to characterize the pharmacokinetics and pharmacodynamics of drotrecogin alfa (activated) (recombinant human activated protein C) in patients with severe sepsis. ⋯ Plasma concentrations of drotrecogin alfa (activated) attain steady state rapidly after the infusion is started and decline rapidly after the infusion is stopped. The infusion rate should be based on predose body weight and not on any other demographic or baseline clinical covariate.
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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.
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Clin. Pharmacol. Ther. · Nov 1994
Randomized Controlled Trial Multicenter Study Clinical TrialCaffeine as an analgesic adjuvant in tension headache.
Six randomized, double-blind, two-period crossover studies, conducted under similar protocols, compared the efficacy of two analgesic combinations containing caffeine with an acetaminophen 1000 mg control and with a placebo in outpatients with episodic tension-type headaches. In four studies, comprising 1900 patients, the caffeine-containing analgesic consisted of a combination of 500 mg acetaminophen, 500 mg aspirin, and 130 mg caffeine (APAP/ASA/CAF). In two studies, comprising 911 patients, the caffeine-containing analgesic consisted of a combination of 1000 mg acetaminophen and 130 mg caffeine (APAP/CAF). ⋯ The significant analgesic adjuvant effect of caffeine was independent of patients' usual caffeine use or their caffeine consumption in the 4 hours before medication. For each treatment, the pooled analgesic responses for the four studies of APAP/ASA/CAF were virtually superimposable on the responses in the two APAP/CAF studies. The combinations produced more stomach discomfort, nervousness, and dizziness than acetaminophen or placebo.
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Clin. Pharmacol. Ther. · Jul 1992
Randomized Controlled Trial Multicenter Study Clinical TrialOndansetron is effective in decreasing postoperative nausea and vomiting.
The efficacy of ondansetron, a selective 5-HT3 receptor antagonist, in preventing postoperative nausea and vomiting in surgical patients was studied. Fifty women were randomized in a double-blind manner to receive either two 8 mg doses of intravenous ondansetron or two doses of placebo vehicle: the first given just before general anesthesia induction and the second 8 hours later. During the first 24 postoperative hours, the number of emetic episodes was recorded and the subjects rated their nausea on a scale from 0 to 10. ⋯ The number of complete responders (no emetic episodes and no rescue therapy) was 1 of 24 (4%) and 15 of 26 (58%) in the placebo and ondansetron groups, respectively (p less than 0.001). Ondansetron is clearly more effective than placebo in the prophylaxis of postoperative nausea and vomiting. The adverse event profile for ondansetron was similar to that of placebo.