British journal of clinical pharmacology
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Br J Clin Pharmacol · Nov 1983
The analgesic effect of the GABA-agonist THIP in patients with chronic pain of malignant origin. A phase-1-2 study.
Fourteen patients with chronic pain of malignant origin were treated with escalating doses of THIP intramuscularly 5-30 mg in an open phase 1 study. Analgesic activity was demonstrated in 60% of the patients at the level of 20 mg THIP and a dose response relation was present. Side effects, sedation, dizziness, euphoria, nausea, and blurred vision were present in up to 80% of the patients and were dose limiting. ⋯ Mean t1/2 was 1.52 +/- 0.63 h and the clearance was 0.49 +/- 0.181 min. Significant correlations were demonstrated between serum concentration, dose of THIP, analgesic effect and side effects. It is concluded that THIP cannot be used for the treatment of chronic cancer pain, not because of insufficient analgesic effect but because of unacceptable side effects.
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Br J Clin Pharmacol · Nov 1983
Active metabolites of acenocoumarol: do they contribute to the therapeutic effect?
The pharmacokinetics and pharmacodynamics of racemic acenocoumarol (AC), the amino (AM) and acetamido (AA) derivative were investigated in healthy volunteers after administration of a single oral (10 mg) dose. All three coumarins were rapidly absorbed from the gastrointestinal tract. The elimination half-lives were 10.9, 10.4, and 4.1 h, for AC, AM and AA, respectively. ⋯ The oral administration of AC resulted in a rise in prothrombin time with a maximum effect at 24 to 30 h. No anticoagulant activity was observed upon the administration of AM and AA. The results indicate that the compounds AM and AA, if they are formed out of AC at all, do not contribute to the anticoagulant activity of AC.