Clinical pharmacology and therapeutics
-
Clin. Pharmacol. Ther. · Oct 2000
Combined phenotypic assessment of CYP1A2, CYP2C19, CYP2D6, CYP3A, N-acetyltransferase-2, and xanthine oxidase with the "Cooperstown cocktail".
Simultaneous administration of several probes enhances the utility of phenotyping, but poor specificity, side effects, and use of drugs not approved by the Food and Drug Administration limit the usefulness of prior phenotyping cocktails. ⋯ These results indicate no pharmacokinetic or pharmacodynamic interactions that would limit the utility of this phenotyping cocktail for simultaneous measurement of the activity of multiple drug-metabolizing enzymes.
-
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.
-
Clin. Pharmacol. Ther. · Sep 2000
Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis.
L-Carnitine is an endogenous molecule involved in fatty acid metabolism. Secondary carnitine deficiency may develop in patients with end-stage renal disease undergoing long-term hemodialysis because of dialytic loss. In these patients L-carnitine can be administered to restore plasma and tissue levels. The objective of this study was to evaluate the pharmacokinetics of intravenous L-carnitine in patients undergoing long-term hemodialysis. ⋯ The study demonstrated that removal of L-carnitine by hemodialysis is extremely efficient and that patients undergoing hemodialysis had plasma concentrations that were substantially lower than normal, particularly during dialysis. During repeated administration of L-carnitine, the predialysis and postdialysis concentrations of the compound increased steadily, reaching an apparent steady state after about 8 weeks. It is proposed that this accumulation arose from the distribution of L-carnitine into a deep tissue pool that includes skeletal muscle.
-
Clin. Pharmacol. Ther. · Sep 2000
Randomized Controlled Trial Clinical TrialEffects of the 2-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid/kainate antagonist LY293558 on spontaneous and evoked postoperative pain.
Previous studies suggest that 2-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA)/kainate antagonists reduce experimentally induced pain. There have been no studies of AMPA/kainate antagonists in clinical pain. ⋯ This is the first evidence that an AMPA/kainate antagonist reduces clinical pain. Tests of evoked pain may be more sensitive to certain analgesics than those of spontaneous pain. The evaluation of evoked pain as an outcome measure in analgesic trials may identify potentially useful compounds otherwise missed if only spontaneous pain is evaluated.
-
Clin. Pharmacol. Ther. · Sep 2000
Effect of hydrocortisone on phenylephrine--mean arterial pressure dose-response relationship in septic shock.
Septic shock is characterized by decreased responsiveness to catecholamines. Because endogenous steroids are known to play a role in the modulation of vasomotor tone, the purpose of our study was to investigate the phenylephrine-mean arterial pressure dose-response relationship in patients with septic shock and the effect of a physiological dose of hydrocortisone on it. ⋯ In patients with septic shock, the Emax of phenylephrine is decreased, whereas its ED50 is not modified, both before and after administration of hydrocortisone. A physiological dose of hydrocortisone tends to normalize the relationship.