Brachial, radial, or femoral approach for elective Palmaz-Schatz stent implantation: a randomized comparison.

UNLABELLED: From October 1994 to November 1995, 150 male eligible patients were randomly assigned to Palmaz-Schatz stent implantation through 6 French catheters using the femoral (puncture) (n = 56), radial (puncture) (n = 56), or brachial (cutdown) (n = 38) approach at 6 participating Belgian centers. Acenocoumarol was given for 1 month after stenting. END POINTS: Primary-entry site complications (bleeding, haematoma, transfusion, occlusion, surgery) poststent implantation. Secondary-success rate, stent thrombosis, Q or non Q wave MI, repeat PTCA, CABG, CVA, haemorrage, death. There were no statistically significant differences between the three groups for base line and angiographic patient characteristics, procedural characteristics, in hospital outcome, average hospitalisation time after stenting, events during the month after stenting, or local complications at 1 month follow-up. The only statistically significant difference was the arterial time of the procedure: mean +/- SD (minutes) brachial 31.0 +/- 10.02 *P < 0.001, femoral 42.2 +/- 21.8, radial 55.8 +/- 31.3 **P < 0.0001 (*brachial vs. femoral, **brachial vs. radial). There was a clear trend toward more technical difficulties and more problems with the radial approach. In each group: vascular surgery at entry site: 0%, blood transfusion: 0%. In our study, local complications and length of hospital stay were similar with the three possible approaches, and brachial approach was associated with a shorter arterial time.

Immediate and long-term results of percutaneous coronary angioplasty in patients aged 70 years or older.

Percutaneous coronary angioplasty (PTCA) nowadays appears as an attractive alternative to coronary artery by-pass grafting not only in young adults, but also in elderly patients. The aim of this study was to investigate the primary success, complications and long-term efficacy of PTCA in a consecutive series of 63 patients aged 70 years or over. Results are analysed in comparison to a younger group of 423 subjects who were submitted to PTCA during the same period of time. In the older group, PTCA was applied to 108 lesions. The angiographic success rate was 88%. Primary success was 87%, with a majority (91%) of complete revascularization. Failure of the procedure was recorded in eight patients (13%). Complications of PTCA were observed in three patients, (among these: one death). The outcome was excellent: out of 55 patients with successful angioplasty, 52 (94.6%) were asymptomatic at the time of hospital discharge. At follow-up (close to one year), 84.6% of the patients remained asymptomatic. The comparison with the younger group of patients showed no difference in terms of primary success, failure rate or incidence of complications. We therefore conclude that PTCA can be performed with safety and efficiency in patients aged 70 years or over.

Comparative effects on hemodynamics of enoximone (MDL 17,043), dobutamine and nitroprusside in severe congestive heart failure.

To assess their comparative effects on hemodynamics, nitroprusside, dobutamine and enoximone were sequentially administered to 10 patients with severe congestive heart failure. Nitroprusside, dobutamine (at 10 micrograms/kg/min) and enoximone (at 2 mg/kg) increased stroke volume index to a similar extent (31%, 34% and 36%, respectively). Enoximone produced less tachycardia than dobutamine and, consequently, a smaller improvement in cardiac index. Mean arterial pressure was not altered by dobutamine but was reduced 9% by enoximone, 2 mg/kg. This finding accounts for the larger (although not significant) increase in left ventricular stroke work index observed with dobutamine compared with enoximone. Ventricular filling pressures and vascular resistances were significantly decreased by all 3 drugs (p = 0.001). All 3 drugs improved cardiac pump function when assessed by the increase in stroke index to a similar extent; however, enoximone (2 mg/kg) resulted in less hypotension than nitroprusside (mean arterial pressure -9% vs -22%, p = 0.0001) and in less tachycardia than dobutamine 10 micrograms/kg/min. Those differences in mode of action account for the variations observed in the heart rate-blood pressure product (dobutamine 10 micrograms/kg/min, +18%, enoximone 2 mg/kg, -5%, p = 0.003). Enoximone thus appears to be of great value in the management of severe congestive heart failure by its combination of vasodilatory and inotropic properties. Enoximone (2 mg/kg) provides a clinically significant increase in cardiac index, a clear reduction of ventricular filling pressures, a moderate reduction of mean arterial pressure and only minor changes of heart rate and of rate pressure product.

Absolute bioavailability of mianserin tablets and solution in healthy humans.

A pharmacokinetic study with mianserin . HCl was performed in six healthy male subjects. The subjects were treated on different occasions intravenously with a constant-rate infusion of 5 mg mianserin. HCl in 1 h, orally with a single dose of 60 mg as two tablets of 30 mg each and with 60 mg as an oral solution. The wash-out period between treatments was 1 month. Blood samples were taken at predetermined times over a period of 120 h following dosing. The mianserin concentration in the plasma samples was determined and the results were pharmacokinetically analyzed. The intravenous data could be adequately described by a 3-compartment model and the oral data by a 2-compartment model, both with first-order transfer and elimination rate constants. The mean plasma clearance of mianserin was found to be 19 +/- 2 l h-1 (mean +/- SEM), the kinetic volume of distribution 444 +/- 250 l, the steady-state volume of distribution 242 +/- 171 l and the elimination half-life 33 +/- 5 h. The absolute bioavailability in terms of extent of absorption was 22 +/- 3% for the solution and 20 +/- 3% for the tablets. The mean peak level for the solution was 79 +/- 11 ng X ml-1 and for the tablets 54 +/- 5 ng X ml-1; mean peak time for the solution was 1.1 +/- 0.2 h and for the tablets 1.4 +/- 0.2 h. The mean absorption half-life for the solution was 0.43 +/- 0.13 h and for the tablets 0.39 +/- 0.11 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic consequences of long term coadministration of cimetidine and triazolobenzodiazepines, alprazolam and triazolam, in healthy subjects.

The influence of administration of cimetidine (1 g daily for 2 weeks) on the pharmacokinetics of alprazolam (0.5 mg t.i.d. for 1 week) and triazolam (0.5 mg nightly for 1 week) was investigated in two groups of 8 healthy subjects. The plasma AUC of these triazolobenzodiazepines were significantly increased. Moreover, for triazolam, the C max was increased and the plasma elimination half-life was prolonged; oral clearance of the two triazolobenzodiazepines was markedly reduced. It is suggested that the combined treatment cimetidine-alprazolam requires a reduced daily dosage (one third) of alprazolam or increased dosage intervals (b.i.d. instead of t.i.d.). For triazolam, used as a hypnotic drug, such dosage reduction appears unsuitable if administered on a once-nightly basis.

Absolute bioavailability of amiodarone in normal subjects.

The relative and absolute bioavailability of different oral forms of amiodarone was examined in 12 subjects. The doses were 5 mg/kg iv, two 200-mg commercial tablets by mouth, two 200-mg tablets (new formulation) by mouth, and 400 mg in a drinkable solution. Plasma levels of amiodarone and its N-desethylated metabolite were determined by HPLC. Statistical analysis indicated bioequivalence of the oral forms for all the kinetic parameters examined. After oral dosing, amiodarone was slowly absorbed and the maximum plasma level (0.55 +/- 0.20 mg/l) was reached in 4.5 hr. The absolute bioavailability of oral amiodarone was calculated by comparison of AUCs after oral dosing with those after intravenous injection. A mean oral bioavailability of 65% +/- 22% was indicated. Since the tablets were bioequivalent to the drinkable solution, incomplete absorption seems not be a result of the dissolution characteristics of the commercial formulation but rather of a first-pass effect.

Effect of fenofibrate and LF 2151 on hepatic peroxisomes in hamsters.

Hamsters were given a diet containing fenofibrate (0.5% or 0.05%) or its metabolite, LF 2151 (0.15% or 0.015%) or a standard diet for a 3-week period. At the end of this period, the analysis of plasma lipids showed that the mean plasma triglyceride concentrations were not significantly different in the five groups of animals. The mean plasma cholesterol concentrations were significantly reduced in animals treated with both drugs but only when given at the high dosage. No consistent changes were noted in the liver weight/body weight ratio and the DNA content of the liver; the number of peroxisomes was increased in the hepatocytes of animals given fenofibrate at the high dosage. Liver homogenates were fractionated and the fractions rich in peroxisomes were used for assays of several enzymes involved in lipid metabolism. Compared with the control animals, activity of cyanide-insensitive fatty acyl-CoA (FA-CoA) oxidizing system was significantly increased by fenofibrate at the high dosage, carnitine acetyltransferase activity was markedly increased by both drugs at the high dosage and catalase activity remained unmodified. As there was a significant inverse correlation between the peroxisomal activity of FA-CoA oxidizing system and the plasma cholesterol concentrations, it is suggested that the increase of peroxisomal beta-oxidation activity can be involved in the hypocholesterolemic action of fenofibrate and LF 2151. This is further substantiated by the finding that fenofibrate and LF 2151 were present in the peroxisomal fraction only in hamsters displaying hypocholesterolemia and high activity of FA-CoA oxidizing system. The presence of fenofibric acid in the plasma of hamsters given LF 2151 suggested that hepatocytes are able to generate the parent drug from this metabolite, underlining that the pharmacokinetics of fenofibrate are rather complex in hamsters.

Fluoride absorption: a comparative study of 1 and 2% fluoride gels.

The systemic fluoride absorption following topical fluoride gel application has been monitored in two groups of 6 healthy volunteers. Plasma F- levels and urinary fluoride excretion were measured after the use of a 1% and of a 2% gel preparation (commercial products). The resorption of these gels seems lower than reported previously for other preparations. Creatinine clearance remained unaffected after a single application of the gels in healthy subjects.

[Peroxisomes and hypolipidemic agents ]. / Peroxysomes et hypolipémiants.

Peroxisomes (microbodies) have been localized in the cytoplasm of various cells, mainly the hepatocytes and the renal tubular cells. Various enzymes were found in the granular matrix and sometimes in the nucleus; they were involved in the production and the degradation of hydrogen peroxide, in regulation of the energetic processes of the cell, and in the oxidation of fatty acids. Several xenobiotica and drugs such as hypolipidemic agents clofibrate-like, have induced in rodents a proliferation of peroxisomes and frequently, the appearance of malignant tumors. In men, the precise role of peroxisomes in the physiology of the cell, their link with the hypolipidemic action of some drugs and the development of cancer remain to be established.

[Peroxisomes and hypolipidemic agents (author's transl)]. / Peroxysomes et hypolipémiants.

Peroxisomes (microbodies) have been localized in the cytoplasm of various cells, mainly the hepatocytes and the renal tubular cells. Various enzymes were found in the granular matrix and sometimes in the nucleus ; they were involved in the production and the degradation of hydrogen peroxide, in regulation of the energetic processes of the cell, and in the oxidation of fatty acids. Several xenobiotics and drugs such as hypolipidemic agents clofibrate-like, have induced in rodents a proliferation of peroxisomes and frequently, the appearance of malignant tumors, in men, the precise role of peroxisomes in the physiology of the cell, their link with the hypolipidemic action of some drugs and the development of cancer remain to be established.