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 120 mg. 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.
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 20 mg. 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 12 h post-infusion, the difference remained between 25 per cent and 73 per cent. Mean AUC0-infinity was statistically greater in patients than in volunteers while mean V area, CLtot, and CLren were statistically lower. The t1/2 alpha and t1/2 beta values were not significantly (p greater than 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 t1/2 beta 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.
A high-performance liquid chromatographic method using a fluorometric detector was developed for the determination of plasma concentrations of the antidepressant indalpine (I) and its major metabolite 4-[2-(3-indolyl)ethyl]-2-piperidinone (PK). the same procedure was used to measure, in urine, levels of I and of the metabolite, either conjugated or unconjugated. The sensitivity of the assay is 5 ng ml-1 of plasma or urine for both I and PK. Mean recoveries from plasma for PK, I, and the internal standard (quinine sulfate) were 86.4, 86.8, and 88.5 per cent, respectively. Mean recovery from urine for I was 82.5%. This method was used to establish the pharmacokinetic profiles of I and PK following a single oral administration of I (100 mg) in 8 healthy volunteers. Peak plasma concentrations for I and PK were obtained in an average time of 2.1 and 2.6 h (tmax), respectively. The mean absorption t1/2 of I was 0.8 h, the mean Vda 878 l and the mean clearance 58 l h-1. The mean t1/2 for I and PK was 10.4 and 11.9 h, respectively. In a 12 h urine collection 3 per cent of I was excreted unchanged. No conjugated or unconjugated metabolite was found in urine samples. This method was also used to determine plasma levels 10 h post-dose (50 mg t.i.d.) during chronic oral administration in 20 hospitalized patients. Mean plasma concentrations of I and PK post-dose were 116 ng ml-1 and 43 ng ml-1, respectively.
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