ABSTRACT
Pregnanolone emulsion was administered i.v. to 13 healthy male volunteers to assess its potential as an agent for i.v. induction of general anaesthesia and to establish a pharmacokinetic profile at two doses. Each subject received 0.5 mg kg-1, 0.75 mg kg-1 and 1.0 mg kg-1 on successive occasions, the rate of administration being constant for each dose. Pregnanolone emulsion was found to produce smooth and reliable induction of general anaesthesia with cardiorespiratory effects comparable to those of other i.v. induction agents.
Subject(s)
Anesthesia, General , Anesthesia, Intravenous , Anesthetics , Pregnanolone , Adolescent , Adult , Anesthetics/pharmacokinetics , Blood Pressure/drug effects , Drug Evaluation , Fat Emulsions, Intravenous , Heart Rate/drug effects , Humans , Male , Pregnanolone/blood , Pregnanolone/pharmacokinetics , Pregnanolone/pharmacology , Time FactorsABSTRACT
1. The potential interaction between racemic warfarin given as a 25 mg single oral dose and chronically administered ketorolac was studied in 12 young healthy male volunteers. 2. Ketorolac produced no major change in the pharmacokinetics of (R)- or (S)-warfarin. 3. Ketorolac did not alter the pharmacodynamic profile of racemic warfarin. 4. Ketorolac increased template bleeding time by a factor of 1.35 as compared with placebo. 5. The results suggest that the ketorolac-warfarin interaction is unlikely to be of major clinical significance; however, combined use of ketorolac and warfarin in patients should be undertaken with due caution and appropriate monitoring.
Subject(s)
Analgesics/administration & dosage , Tolmetin/analogs & derivatives , Warfarin/pharmacology , Warfarin/pharmacokinetics , Adult , Analgesics/pharmacology , Blood Proteins/metabolism , Double-Blind Method , Drug Interactions , Factor VII/analysis , Humans , Isomerism , Ketorolac , Male , Metabolic Clearance Rate , Prothrombin Time , Tolmetin/administration & dosage , Tolmetin/pharmacology , Warfarin/administration & dosage , Warfarin/bloodABSTRACT
To assess if any pharmacokinetic or pharmacodynamic interaction at steady-state occurs between the new antidepressant tianeptine and a benzodiazepine (oxazepam) following multiple oral dosing of both drugs, 12 healthy male volunteers entered a balanced three-way double blind cross-over study. Tianeptine (12.5 mg) and/or oxazepam (10 mg) were given three times daily for 4 days. Pharmacokinetic data within a dosing interval at steady-state showed that there were no statistically significant changes in the pharmacokinetics of either tianeptine (and its two major metabolites) or oxazepam when both drugs were co-administered. Psychometric data showed that there was no synergistic negative interaction between the two drugs and that their combination may result in beneficial effects on "alertness" and "happiness".
