Maximal blood concentration (Cmax), time to concentration peak (Tmax), area under the serum concentration-time curve (AUC infinity) and half-life (t1/2) after the oral administration of zopiclone 7.5 mg were compared in patients with severe renal failure (group I), with moderate renal insufficiency (group II), and in healthy volunteers (group III) over a 72-h period. Cmax did not differ from one group to the other but Tmax was significantly longer in group II. Half-lives were longer in renal patients than in healthy volunteers and AUC infinity s tended to increase with the degree of renal failure. Hemodialysis of the severely ill renal patients did not increase the plasma clearance of zopiclone. Finally, only small amounts of drug were found in urine in the three groups. Overall, results allow the conclusion that zopiclone may be safely used in patients with various degrees of renal impairment.
The response of the isolated amphibian urinary bladder to thirty-four structural analogs of arginine vasotocin was determined in an effort to define the physiological significance of specific structural groups on the hormone molecule. All but one of the analogs tested possessed full intrinsic activity in this system but varied greatly in their affinity for the receptor site. An analysis of the effect of changes in hydrogen ion concentration upon the response of the bladder to oxytocin was performed in order to determine the number and nature of the ionizable groups involved in hormone receptor interaction. Two ionizable groups with apparent pK's of 7.1 and 7.75 were found to be important in determining the magnitude of the hormonal response. On the basis of the results it was postulated that hormone-receptor interaction can be considered a two-step process: (a) The binding or attachment of hormone to receptor site through ionic, hydrogen, and hydrophobic bonds and (b) a disulfide interchange reaction between hormonal disulfide and receptor sulfhydryl. The latter step is considered to be the reaction which initiates the chain of events leading to the observed change in permeability.
Abstract The pharmacokinetics of oral diltiazem were studied in 10 patients with chronic renal failure not requiring dialysis and in five healthy volunteers after a single dose of 120mg. We found that patients with chronic renal failure had lower amounts of unchanged diltiazem and of its main metabolite (MA) in urine and a trend to have slightly higher values of plasma concentration. Since the terminal elimination phase is not affected by chronic renal failure we conclude that this trend is probably the result of alterations in the volume of distribution of diltiazem in these patients.
Abstract The pharmacokinetics of diltiazem were studied in seven patients with chronic renal failure (CRF) not requiring dialysis and in three healthy volunteers after a rapid i.v. infusion of 20mg. Mean plasma concentrations at the end of infusion were 3·15 times higher in patients with CRF than in healthy volunteers. From 0·5 to 12h post‐infusion, the difference remained between 25 per cent and 73 per cent. Mean AUC 0–∞ was statistically greater in patients than in volunteers while mean V area, CL tot , and CL ren were statistically lower. The t 1/2α and t β values were not significantly ( p > 0·05) different between patients and volunteers. Renal excretion was statistically more important in volunteers (6·6 per cent of the dose) than in patients (1·2 per cent of the dose). We therefore conclude that CRF does not influence t 1/2β of diltiazem but it interferes with the extent and possibly the rate of its extravascular distribution. That could result in transient high plasma concentrations after rapid i.v. infusion.
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