European journal of clinical pharmacology
-
Eur. J. Clin. Pharmacol. · Jan 1988
Clinical Trial Controlled Clinical TrialPossible site of bronchodilation due to inhaled procaterol aerosol in asthmatic patients.
We studied the effective site of an inhaled aerosol of procaterol, a beta 2-selective adrenergic bronchodilator, in 8 asthmatic patients whose basal lung functions are almost within the normal range in both slow vital capacity (VC) and forced expiratory volume in one second (FEV1.0), and are free from asthmatic attack. In patients who had received procaterol 30 min after inhalation of aerosol, there was no significant change in VC, although FEV1.0, maximal expiratory flow at 50% VC (V50), maximal expiratory flow at 25% VC (V25) and maximal expiratory flow at 30% VC of partial maximal expiratory flow volume curve (V30p) improved significantly. ⋯ After an interval of 5 min, R1 did not change any further, while C0.5 continued to improve until 30 min after inhalation of procaterol. These results suggest that procaterol may first dilate the large airway and then may gradually dilate the small airway in bronchial asthma.
-
Eur. J. Clin. Pharmacol. · Jan 1988
Comparative StudyCSF and plasma pharmacokinetics of pethidine and norpethidine in man after epidural and intrathecal administration of pethidine.
The disposition of pethidine and its main metabolite, norpethidine, in cerebrospinal fluid (CSF) and plasma was studied in 11 thoracic surgery patients after lumbar epidural (100 mg; n = 6) or lumbar intrathecal (25 mg; n = 5) administration of pethidine. Pethidine appeared more slowly in plasma after intrathecal than after epidural administration (tmax 2.3 h and 14 min, respectively), but systemic bioavailability was similar. The CSF concentrations of pethidine were higher than those in plasma after both routes of administration. ⋯ The terminal elimination half-life of pethidine was 6.0 h (CSF) and 5.4 h (plasma) after intrathecal administration and 8.6 h (CSF) and 8.8 h (plasma) after epidural injection. The volume of distribution of unchanged pethidine in the subarachnoid space was 13 ml.kg-1 and clearance from the CSF was 15 microliters.kg-1.min-1. In all patients receiving intrathecal pethidine and in some patients after epidural pethidine, CSF norpethidine concentrations were higher than those in plasma; the maximum CSF norpethidine was 102 to 1211 ng.ml-1 and 14 to 210 ng.ml-1 and the maximum CSF/plasma norpethidine concentration ratios were 21 to 652 and 0.6 to 14 times after intrathecal and epidural administration, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
-
Eur. J. Clin. Pharmacol. · Jan 1988
Pharmacokinetics of ketorolac tromethamine in humans after intravenous, intramuscular and oral administration.
The pharmacokinetics of ketorolac tromethamine, a potent non-narcotic analgesic agent used for relief of moderate to severe pain, has been studied in 15 healthy volunteers who received single 10 mg doses intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.) in a three-way cross-over design. The kinetics of i.v. ketorolac were characterized by a terminal half-life of 5.09 h, a small plasma clearance (CL = 0.35 ml.min-1.kg-1) and a small tissue distribution (Vss = 0.11 l.kg-1, V beta = 0.17 l.kg-1; mean (SD). Following i.m. and p.o. administration, peak levels of approximately 0.8 microgram/ml were rapidly attained (tmax = 0.8 and 0.9 h, respectively) and the systemic bioavailability was essentially complete.
-
Eur. J. Clin. Pharmacol. · Jan 1988
The effect of cardiopulmonary bypass on plasma protein binding of alfentanil.
The effect of cardiopulmonary bypass (CPB) on plasma concentration and protein binding of alfentanil was studied during continuous infusions in five cardiac surgical patients. Patients were given a loading infusion of 10 micrograms.min-1.kg-1 lean body mass (LBM) over 30 s followed by a fixed rate maintenance infusion of 1 microgram.min-1.kg-1 LBM for the duration of surgery. Prior to the commencement of CPB the total plasma alfentanil concentration was 177 micrograms.l-1. ⋯ The unbound concentration prior to CPB was 29 micrograms.l-1 and was essentially unchanged by the onset of CPB, being 35 micrograms.l-1 at two min and then 31 micrograms.l-1 at the end of CPB. There was a good correlation between alfentanil bound/unbound concentration ratio and plasma albumin concentration (r = 0.57) and plasma alpha 1-acid glycoprotein concentration (r = 0.80), indicating that the decrease in binding during CPB was due primarily to haemodilution. In assessing the effects of CPB on plasma drug concentrations, it is therefore necessary to monitor unbound as well as total concentrations because the effects on these differ greatly.
-
Eur. J. Clin. Pharmacol. · Jan 1988
The effect of a diet rich in brussels sprouts on warfarin pharmacokinetics.
Ten healthy subjects were given 20 mg of warfarin orally before, and after a daily intake of 400 g of brussels sprouts for 2 weeks. The brussels sprouts diet stimulated warfarin disposal as evidenced by a 29% increase in mean elimination rate constant, accompanied by a 27% increase in metabolic clearance rate and a 16% decrease in plasma AUC. It is concluded that a high intake of brussels sprouts, a cruciferous vegetable, accelerates warfarin disposal, and thereby might contribute to less anticoagulation.