Plasma turnover and excretion of K-strophanthoside-3H in human volunteers after parenteral administration.

Pharmacokinetic parameters of K-strophanthoside-3H, a short-acting cardiac glycoside, were investigated in healthy subjects, patients suffering from heart disease, renal failure and in cholecystectomized patients with a biliary T-tube inserted surgically, after parenteral administration of 250 mug of the glycoside. The healthy subjects, patients suffering from heart disease and those with the biliary T-tube showed a dominant half-time for plasma turnover of the glycoside of 15-16 h after the i.v. route and 18-22 h after the i.m. route and cumulative urinary excretion of the drug over a 24 h period of 37-42% (i.v. route) and 32-33% (i.m. route). The volumes of distribution were lower in patients with heart disease and patients with biliary fistula than in the healthy subjects. In patients suffering from renal failure the dominant half-time of plasma turnover was higher (33 h), while cumulative urinary excretion of the glycoside (12%) and the volumes of distribution were lower than in the healthy subjects. A peak of plasma levels 30 min after i.m. administration of K-strophanthoside-3H leads to the conclusion that this glycoside is rapidly absorbed when injected intramuscularly.

Influence of food on the absorption of flurithromycin in man.

Oral absorption of flurithromycin, a new fluorinated macrolide, has been evaluated on eight healthy volunteers on fasting and after a standard meal. Serum levels from 0 to 8 hours, peak serum concentrations, times to peak and areas under the curves were compared using a balanced sequence cross-over design. The highest mean concentration was reached after 3 h from administration on fasting (1.36 +/- 0.31 mcg/ml) and after 1 h following a meal (1.36 +/- 0.30 mcg/ml). All the pharmacokinetic parameters considered showed no statistical change. Therefore a meal does not reduce or delay the absorption of flurithromycin, while in the presence of food other macrolides may behave differently. Moreover the tolerability to the drug was good, lacking any report of side-effects, either on fasting or after the food.

Comparative evaluation of three dosages of slow-release isosorbide dinitrate (60, 80, 100 mg) in chronic angina of the aged.

In a single-blind, placebo-controlled study the acute and chronic antianginal effects of three slow-release (SR) new formulations of isosorbide dinitrate (ISDN 60, 80, 100 mg) have been comparatively evaluated in a group of aged affected by chronic stable effort-induced angina. Compared to placebo, overall the active dose paritetically improved the effort tolerance up to 24 h after the first assumption. In the time course of the trial (2 and 4 weeks) the resting hemodynamic changes induced by the first dose were partially blunted without affecting the exercise related-parameters. Also if plasma levels of ISDN and of its metabolites did not correlate to the degree of physical improvement, the peak increase in effort tolerance was observed under 100 mg treatment. Mild to moderate transient headache was experienced by 50% of actively treated and by 20% of placebo treated patients and no other serious adverse effects have been noted. One may conclude that ISDN in slow-release formulations of 60-100 mg isan effective, safe and well tolerated medication in the management of angina in the aged.

Does aortic regurgitation affect transmitral flow? An echo-Doppler study.

Recent studies suggest that the presence of aortic regurgitation can interfere with Doppler measurement of mitral pressure half-time in patients with mitral stenosis. Amongst the factors affecting the transmitral flow in aortic regurgitation a putative role may be played by the mechanical hit of the aortic regurgitant jet impinging on the anterior mitral leaflet, as is very often seen with Doppler Color Flow examination. This study was designed to evaluate the effects of pure aortic regurgitation on the transmitral flow in patients with normal mitral valves. We studied 35 patients affected by pure chronic aortic regurgitation but with a normal mitral valve and compared them with 30 normal subjects. In all the patients the aortic regurgitant jet was directed toward the anterior mitral leaflet. In all the patients and control subjects a standard echo-Doppler examination was performed, sampling the transmitral flow at the level of the tip of the mitral leaflets. In 7 patients and 11 normal subjects the transmitral flow was also sampled at the level of the mitral annulus. Patients with aortic regurgitation showed significantly higher values of the mitral pressure half-time (61.04 +/- 15.14 vs 50.59 +/- 7.07 ms, P < 0.05) and of the time-velocity integral of the total transmitral flow, while the other parameters of transmitral flow, the mitral annulus diameter and the mitral stroke volume didn't show statistically significant differences. The comparison of the pressure half-time and time-velocity flow values measured at the level of the mitral annulus between patients and normal subjects didn't show significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmacokinetics of defibrotide in uremic patients undergoing hemodialysis]. / Farmacocinetica di defibrotide in pazienti uremici sottoposti ad emodialisi.

Defibrotide pharmacokinetics were studied in 6 voluntary healthy subjects and in 10 uremic patients undergoing dialysis during which (instead of heparin) defibrotide was administered to prevent fibrino-formation in the circuit. Blood concentrations of the drug were assessed (expressed with reference to the residual glycidic deoxyribose) during a standard dialysis using defibrotide, 3.5, 15, 30, 45, 60 and 90 minutes after the defibrotide bolus (200 mg) had been injected into the arterial channel. The half-lives of the alpha and beta plasmatic phases were found to be equal at 3.79 and 41.4 min in dialysed subjects and at 1.13 and 16.54 in healthy volunteers. These results indicate that in uremic patients undergoing dialysis at intervals using defibrotide, a longer time is required to eliminate the drug from the circulation. This variation does not however appear to be significant in terms of the therapeutic use of the drug during dialysis.

[Arrhythmias in the mitral valve prolapse syndrome]. / Studio delle aritmie nella sindrome del prolasso della mitrale.

Possible connections have been investigated between PVc (premature ventricular contractions) and echocardiographic patterns in 23 patients affected by MVPS. Pansystolic prolapse has been found in 12 cases and mid-systolic prolapse in 11. A correlation has been found between significant ventricular arrhythmias (50 PVc/24 h) and mid-systolic prolapse. These findings suggest the mechanical origin of cardiac rhythm disorders.

Gas chromatographic evaluation of trapidil and its desethyl metabolite in biological fluids for pharmacokinetic and bioavailability investigations.

This paper describes a suitable and cost-saving method for quantitative analysis of trapidil (5-methyl-7-diethylamino-s-triazolo [1,5-a]pyrimidine) and its desethyl metabolite in plasma and urine for pharmacokinetic and bioavailability investigations. Trapidil and desethyl-trapidil were extracted from plasma, concentrated and injected into the gas chromatography without any derivatization process. The authors suggest a series of internal standards. A thermoionic specific detector enables high sensitivity to be achieved, i.e. 20 ng/ml, and good specificity. The method is cost-saving in that it allows about 30 analyses a day to be performed without automatic integrators, and about 50 analyses a day with these integrators.

Single-dose pharmacokinetics of fenquizone in healthy volunteers.

A pharmacokinetic study of fenquizone (Idrolone), a thiazide-like diuretic, was conducted with single oral doses in 6 healthy volunteers. The substance thus administered was readily absorbed from the gut, with peak plasma levels being detected on average at 3 h after dosing; after that, plasma concentrations of fenquizone decreased biexponentially in a pattern fitting an open two-compartment model. Plasma half-life values were 1 h for phase alpha and 17 h for phase beta. The half-life calculated from urinary concentrations was 18 h. The apparent distribution volume for phase beta was 686 l; renal clearance was 220 ml/min, and the absorption constant (Ka) was 1055 h-1. Cumulative urinary excretion accounted for 53.1% of the administered dose in 72 h. Thus the pharmacokinetic profile of fenquizone was that of an "intermediate-acting" diuretic about half-way between the short-acting hydrochlorothiazide, chlorothiazide and furosemide and the long-acting chlorthalidone. In summation, fenquizone is described as a low-dosage diuretic apparently not conducive to accumulation; its pharmacokinetic profile qualifies the product particularly well for maintenance therapy, such as is needed for the management of essential hypertension, both as sole medication and in fixed-ratio combination with beta-blockers, and at any rate with once-a-day administration.

[Respiratory effects of PGI-2 in the pig]. / Effetti respiratori della PGI2 nel maiale.

In anaesthetised pig the intravenous perfusion of 2 micrograms/Kg/min/4 min of PGI2 induces within 30'' respiratory changes that spontaneously disappear after perfusion. The PGI2 induces a decrease of respiratory frequency while total pulmonary resistance increases significantly. This changes of pattern of breathing are correlated to tonus of vagus nerve and after vagosimpathectomy are not present. The relationship of tidal volume/frequency has been evaluated according to the blood pressure variation.

[Hemodynamics in swine treated with PGI 2]. / Emodinamica nel maiale trattato con PGI2.

The hemodynamic response of pig perfused by PGI2 (2 micrograms/kg/mm/4 min) has been studied before and after vagosympathectomy. Prostacyclin produces hypotension, which depends to an reduction of total peripheral resistances, without cardiac involvement. A venous dilatation is also present with reduction of preload and of systolic volume. The authors conclude assessing that prostaciclyn act by peripheral mechanism.

Papaverine blood levels after administration of a sustained-release preparation. Short communication.

The authors report the papaverine blood levels obtained after administration to a group of volunteers of a sustained-release preparation in comparison with a conventional form. The new preparation shows bioavailability equivalent to a normal papaverine but substantially more prolonged papaverine blood levels.

Effect of ibopamine on heart rate and spontaneous premature ventricular beats in patients with angina pectoris.

Seven male patients suffering from angina pectoris with spontaneous premature ventricular beats were given oral ibopamine 50 mg t.i.d. for 5 consecutive days, after at least 6 days of observation under basal conditions. A number of clinical parameters were explored during the basal and treatment periods, including repeated 24-hour Holter recordings in each case. The heart rate, expressed as mean hourly rate, minimum and maximum values per observation period, and nocturnal value, showed no clinically or statistically significant change with treatment. There was no worsening of pre-existing arrhythmias or chest pain. All other test parameters remained unchanged. This confirms the excellent tolerance of ibopamine in patients with ischaemic heart disease.