Search PubMed⌕ Search

Biomedical subjects

E Strocchi

Publications and source records attributed to E Strocchi.

At least 37 records · Page 2Linked to original sources
PubMed1992

Weekly doxorubicin chemotherapy for breast cancer in pregnancy. A case report.

The simultaneous occurrence of breast cancer and pregnancy is rare. Little data are available about cytostatic treatment in patients with breast cancer during pregnancy. We report on a 31-year-old woman with a 28-week pregnancy and a T3 N+ Mx breast cancer treated with weekly doxorubicin chemotherapy. This was a well tolerated treatment without toxicity or complications for the mother. A partial response of the tumor was observed after 4 treatment courses. A normal baby was delivered. Doxorubicin and its metabolites were not detected in amniotic fluid collected through amniocentesis. Macroscopic and pathologic examinations of the placenta were normal. Although larger experiences are needed, weekly doxorubicin seems to yield satisfactory results without additional risks of fetal distress or malformations when given in women during the second and third trimester of pregnancy.

Adult↗
PubMed1992

High-performance liquid chromatographic analysis of idarubicin and fluorescent metabolites in biological fluids.

A specific, sensitive, and reliable high-performance liquid chromatographic (HPLC) method for the determination of idarubicin (IDA) and its known fluorescent metabolites idarubicinol (IDAol) and 4-demethoxy-daunomycinone (AG1) in biological fluids (human plasma and urine) was developed and tested. Plasma samples were solid-phase-extracted (C18 bonded silica cartridges). Complete separation of unchanged drugs and metabolites was achieved on a Cyanopropyl chromatographic column (25 cm x 4.6 mm inside diameter; particle size, 5 microns) using fluorescence detection (excitation wavelength, 470 nm; emission wavelength, 580 nm). Sensitivity was better than 0.2 ng/ml for all analytes; rates of recovery of unchanged drug and metabolites were better than 84.5% (IDA), 80.3% (IDAol), and 83.9% (AG1). The interassay coefficient of variation was 6.5% for IDA, 5.8% for IDAol, and 9.8% for AG1. Mean intra-assay precision was 4.6% for IDA, 5.9% for IDAol, and 5.0% for AG1 at sample concentrations of above 1 ng/ml and 12.1% for IDA, 10.8% for IDAol, and 14.1% for AG1 at sample concentrations of below 1 ng/ml.

Calibration↗
PubMed1992

Idarubicin metabolism and pharmacokinetics after intravenous and oral administration in cancer patients: a crossover study.

The pharmacokinetics and metabolism of 4-demethoxydaunorubicin (idarubicin, IDA) were studied in 21 patients with advanced cancer after i.v. (12 mg/m2) and oral (30-35 mg/m2) treatment according to a balanced crossover design. Patients were divided into four groups: subjects who showed normal liver and kidney function (group N), those who presented with normal kidney function and liver metastases (group L), those with kidney dysfunction (creatinine clearance, less than or equal to 60 l/h; group R), and those with both liver and kidney dysfunction (group LR). Five patients showed variations in liver or kidney function after the first treatment and were considered to be nonevaluable for the crossover study but evaluable for the liver/kidney function study; some of them appeared in different groups for the i.v. as opposed to p.o. treatments. After i.v. administration, IDA plasma levels followed a triphasic decay pattern. The main metabolite observed in all patients was the 13C-reduced compound (IDAol), which attained plasma levels 2-12 times higher than those of the parent compound. IDA pharmacokinetics was not dependent on the presence of liver metastases but was related to the integrity of kidney function. Analysis of variance indicated a significant correlation between IDA plasma clearance and creatinine clearance; it was also found that IDA plasma clearance was lower in patients whose creatinine clearance was less than 60 ml/min [group N, 122.8 +/- 44.0 l/h; group L, 104.4 +/- 27.7 l/h (P = 0.58) vs group R, 83.4 +/- 18.3 l/h (P = 0.037)]. The IDAol terminal half-life and mean residence time (MRT) were significantly increased in patients with impaired kidney function [MRT: group N, 63.6 +/- 10.8 h; group L, 69.9 +/- 10.2 h (P = 0.27) vs group R, 83.2 +/- 10.9 h (P = 0.025) and t1/2 gamma: group N, 41.3 +/- 10.1 h; group L, 47.0 +/- 7.4 h (P = 0.31) vs group R, 55.8 +/- 8.2 h (P = 0.025)]. After oral treatment, drug absorption occurred during in the first 2-4 h after IDA administration; a biphasic decay pattern was observed thereafter. The main metabolite observed in all patients was again IDAol. The AUC of IDAol was greater after oral administration than after i.v. treatment in proportion to the AUC of IDA (i.v.: AUC-IDAol/AUC-IDA, 2.4-18.9; p.o.: AUC-IDAol/AUC-IDA, 4.1-21.4). Following oral dosing, a substantial amount of 4-demethoxydaunomycinone (AG1) was found in 11/21 patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1992

ACE inhibition in diabetic patients: effect on pressor responsiveness to noradrenaline.

The pressor responsiveness to noradrenaline was assessed before and after four weeks of treatment with enalapril (20 mg/day) in eight mild-to-moderate essential hypertensives, in eight normotensive type II diabetics and in eight mild-to-moderate hypertensive type II diabetic patients. The ACE inhibitor interfered to the same extent with the renin-angiotensin system and did not alter noradrenaline kinetics in the three groups of patients, but significantly reduced the arterial responsiveness only in non-diabetic subjects. It is suggested that factors, such as an exaggerated sodium retention, might determine the lack of effect of enalapril in diabetic patients.

Adult↗
PubMed1991

The effect of ace inhibition on peripheral hemodynamics in normotensive and hypertensive patients with type II diabetes.

The effect of treatment with enalapril (10 days at 10 mg/d followed by 4 weeks at 20 mg/d) on forearm hemodynamics was assessed in eight normotensive patients and eight patients with hypertension affected by Type II diabetes as well as in eight patients with essential hypertension and normal glucose tolerance. The ACE inhibitor decreased regional vascular resistances and increased the maximum arteriolar-vasodilating capacity and venous distensibility in the three groups of patients. Thus, this study shows that ACE inhibition by enalapril improves regional hemodynamics in patients with Type II diabetes.

Adult↗
PubMed1991

Flecainide: evidence of non-linear kinetics.

The pharmacokinetics of flecainide has been studied in 12 patients with ventricular arrhythmias, both after single administration and during chronic treatment. Both the half-life and the AUC were significantly increased during chronic treatment. This suggests that the kinetics of flecainide might be non-linear also in patients with normal kidney and liver function. The increase in plasma flecainide levels during chronic treatment could not be predicted, so close monitoring of its plasma levels is advisable.

Adult↗
PubMed1991

Aminoglutethimide in advanced breast cancer: plasma levels and clinical results after low and high doses.

Drug plasma levels, metabolism data and clinical results were evaluated after the daily administration of either 500 or 1,000 mg aminoglutethimide (AG, Orimeten, Ciba-Geigy) plus hydrocortisone acetate (20 mg b. i. d.). A total of 34 patients with advanced breast cancer entered the study: 17 were given 1,000 mg/day and 17 received 500 mg/day for at least 3 months. A novel HPLC method was developed to determine the levels of AG and its known metabolites [N-acetyl-AG (NAG), formyl-AG, nitroglutethimide, hydroxy-AG] in the biological samples. AG plasma concentration was significantly higher during the 1,000-mg/day regimen. NAG was the only metabolite observed in plasma, always occurring at concentrations lower than those of the parent drug. The ratios between NAG and AG levels distinguish two statistically different groups of patients. Irrespective of the dose, a partial response was observed in 44% of the patients; no change in 32% of cases; and progressive disease had an incidence of 24%. The probability of response was not dependent on the drug AUC or on the NAG/AG ratio and did not significantly depend on previous hormone treatment. Neither the plasmatic level of the AG or metabolite concentrations nor the NAG/AG ratio seemed to affect the incidence of side effects.

Adult↗
PubMed1991

Pharmacokinetics of a controlled release preparation of naproxen.

The pharmacokinetics of a controlled release preparation of naproxen (750 mg) was compared with that of standard release naproxen, in 12 healthy volunteers. The plasma levels of naproxen and urinary recoveries of naproxen and metabolites were determined both after single doses and chronic administration. The experimental data show that the bioavailability of the controlled release preparation is equal to that of standard release naproxen; however, the controlled release preparation allows more constant plasma levels of naproxen and, when administered once a day for prolonged periods, is capable of maintaining effective concentrations for most of the dosing period.

Adult↗
PubMed1991

[Significance of the degree of oxidative hepatic metabolism in conditioning the pharmacokinetics and the pharmacodynamics of propafenone].

The aim of this study was to evaluate plasma concentrations of propafenone (P) and 5-hydroxy-propafenone (5-OH-P) at steady state in 36 patients with ventricular premature beats, Lown class greater than or equal to 2, submitted to antiarrhythmic treatment with propafenone either in acute administration (AA) (300-450 mg) or in chronic administration (CA) (150-300 mg t.i.d. for 14-21 days followed by a wash out), and to define the relationship existing between metabolic oxidative capacity and P and 5-OH-P pharmacokinetics and pharmacodynamics. Antiarrhythmic treatment resulted efficacious in 31/36 cases (86%) during AA and in 28/36 cases (78%) during CA. At steady state a wide interindividual variability was observed in plasma concentrations of P (mean = 835 +/- 619 ng/ml, coefficient of variation = 74%), in plasma concentrations of 5-OH-P (mean = 142 +/- 93 ng/ml, coefficient of variation = 65%) and of their ratio (mean = 6.51 +/- 8.53, coefficient of variation = 131%), without significant differences between responders and nonresponders. In a subgroup of 14 subjects, characterized as extensive oxidizers of dbrisoquine, a significant correlation (r = 0.97, p less than 0.001) was observed between the ratio of P and 5-OH-P plasma concentrations at steady state and oxidative metabolic capacity (expressed as debrisoquine/4-hydroxy-debrisoquine ratio). Oxidative metabolic capacity was also correlated with P half life (r = 0.82, p less than 0.002 in AA and in CA) and with the ratio of P and 5-OH-P area under curve (r = 0.91, p less than 0.001 in AA and r = 0.90) changes at the electrocardiogram (mean values = + 20% for QRS, +26% for PR). In conclusion, oxidative metabolic pathway is a crucial point in propafenone metabolization; indeed the extent of metabolic oxidative capacity, evaluable by analysis of debrisoquine oxidation, is responsible for a wide interindividual variability of P and 5-OH-P plasma concentrations, present even in a population of debrisoquine extensive oxidizers and, moreover, influences the extent of electrocardiographic changes of PR and QRS intervals, which are related to 5-OH-P plasma levels, but not to P plasma levels.

Adult↗
PubMed1990

ACE inhibition and pressor responsiveness to norepinephrine in hypertensive patients.

The pressor response to norepinephrine (NE) was assessed in normal renin essential hypertensive patients before and after they were randomly assigned to receive in parallel groups of treatment a single dose of an angiotensin converting enzyme (ACE) inhibitor (captopril or lisinopril) or a prolonged therapy with lisinopril (30-45 days) or with hydrochlorothiazide (9 days). Blood pressure was significantly reduced by all treatments. The pressor response to NE was unchanged after the single administration of the ACE inhibitors, while it was blunted after chronic administration of lisinopril and after the diuretic. On the basis of these results, it is suggested that the attenuation of the sympathetically mediated vasoconstriction may represent an additional mechanism contributing to the antihypertensive effect of ACE inhibitors administered chronically.

Adult↗
PubMed1990

Minimal effective concentration values of propafenone and 5-hydroxy-propafenone in acute and chronic therapy.

We evaluated the antiarrhythmic efficacy and the minimal effective concentrations of propafenone and its metabolite 5-hydroxy-propafenone during a) acute intravenous infusion (1.5 mg/kg in bolus followed by 45 minutes infusion), b) an acute oral single-dose test (450 mg), and c) 14-day chronic therapy (300 mg tid) followed by a washout. Oxidative metabolism was assessed by a debrisoquine oral test in every patient. Eleven patients with stable ventricular premature beats (VPBs) greater than or equal to 300/hr and Lown class greater than or equal to 3 completed the study. The main results emphasized a certain discrepancy between the clinical effect of the acute intravenous infusion (efficacy in 5 out of 11 patients) and of the acute oral test and chronic therapy (efficacy in 11/11), with a time lag of the ECG changes during the acute intravenous infusion. The minimal effective concentrations were lower after acute oral administration compared with chronic treatment both for propafenone (200 +/- 189 ng/ml vs. 492 +/- 530 ng/ml; p less than 0.05) and for 5-hydroxy-propafenone (82 +/- 40 ng/ml vs. 149 +/- 80 ng/ml; p less than 0.02). A linear correlation was demonstrated between drug/metabolite ratios of propafenone and debrisoquine, either after acute oral (r = 0.91) or after chronic administration (r = 0.84). The pharmacokinetics of propafenone was nonlinear and showed wide interindividual variations.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Pharmacokinetics of heparin and low molecular weight heparins.

The main kinetic features of heparin and low molecular weight heparins (LMWHs) are reviewed. The complexities related to the study of a nonhomogeneous drug containing fractions with different molecular weight and pharmacological effects are discussed along with the possible bias due to the prevalent use of indirect measures of drug concentration. Available data show that LMWHs have longer half-lives with respect to that of heparin and higher bioavailabilities after subcutaneous administration; experimental and clinical evidences suggest that the kinetics of heparin and LMWHs can only be described taking into account the presence of an endogenous pool from which these drugs are released with different speeds and after various types of manipulations.

Animals↗
PubMed1990

Angiotensin converting enzyme inhibitors, thiazide diuretics and magnesium balance. A preliminary study.

Serum and mononuclear cell magnesium content were determined in a cross-sectional study performed in four groups of hypertensive patients on chronic treatment with atenolol (n = 11), enalapril (n = 10), thiazide diuretics (n = 12), or enalapril + thiazides (n = 11). Our study shows that in patients treated with the thiazides alone, in spite of normal serum potassium and magnesium levels, mononuclear cell magnesium was decreased. To the extent that mononuclear Mg content mirrors the body ion stores, our results indicate that thiazides induce a Mg depletion not detectable by monitoring serum levels.

Adult↗
PubMed1990

[Determination of oxidative phenotype in a sample population and correlation with the pharmacokinetics of propafenone].

UNLABELLED: Propafenone, like other cardioactive drugs (metoprolol, propranolol, encainide) is submitted to oxidative metabolism, evaluable by assessment of debrisoquine oxidative capacity. Two phenotypes have been described: extensive and poor oxidizers, with interethnic differences in the prevalence of poor oxidizers. Aims of this study were: 1) to assess the oxidative phenotype in a sample of the Italian population and 2) to evaluate the relationships between oxidative capacity and propafenone pharmacokinetics or pharmacodynamics. The ratio between debrisoquine (D) and 4-hydroxy-debrisoquine (4-OH-D) in the urines after D administration (10 mg) was employed to characterize oxidative phenotype in 90 subjects (42 arrhythmia patients and 48 healthy volunteers). In 10 patients, extensive oxidizers of debrisoquine, we studied propafenone (P) and 5-hydroxy-propafenone (5-OH-P) kinetics after acute oral administration (450 mg) and chronic oral treatment (300 mg tid for 2 weeks), followed by wash out. RESULTS: 1) the prevalence of poor oxidizers (D/4-OH-D ratio greater than 12.6) in our population resulted to be 6.6%, like in other studies in Caucasians; 2) propafenone kinetics was strictly related to oxidative capacity since D/4-OH-D ratio strictly correlated with the ratio of P and 5-OH-P areas under curve in acute (r = 0.91) and in chronic administration (r = 0.90) and with P half-life in acute (r = 0.82) and in chronic administration (r = 0.82); 3) QRS widening both during chronic treatment and after acute administration correlated with oxidative capacity (r = -0.78 and -0.68 with D/4-OH-D ratio respectively) and with 5-OH-P areas under curve (r = 0.84 and 0.70 respectively); it did not correlate with P areas under curve. In conclusion both kinetics and electrophysiological effects of propafenone strictly correlate with oxidative capacity, even in extensive oxidizers. Thus even a small reduction in oxidative capacity may have relevant consequences during propafenone oral treatment.

Adult↗
PubMed1989

Interaction study of fenoldopam--digoxin in congestive heart failure.

The potential interaction between fenoldopam, a DA1 selective agonist, and digoxin has been studied in 10 patients with heart failure (NYHA Class II or III) on chronic digoxin treatment. Plasma levels and urinary recovery of the glycoside were monitored for 24 h before and after 9 days of treatment with fenoldopam 100 mg tid. Fenoldopam caused a small, non-significant decrease in the mean steady state plasma concentration and area under the plasma concentration curve of digoxin. As the clearance of digoxin was unchanged there does not appear to be an interaction between fenoldopam and digoxin at the level of the renal tubule.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

The incidence of cough during treatment with angiotensin converting enzyme inhibitors.

The incidence of cough during treatment with angiotensin converting enzyme (ACE) inhibitors was studied using retrospective analysis of outpatient records and a questionnaire; for a more precise evaluation, all reported cases of cough were reviewed according to criteria for the operational assessment of side effects, and those found unrelated were excluded. Cough during treatment with ACE inhibitors appears to be more frequent than previously recorded and substantial differences between patients treated with captopril or enalapril seem unlikely.

Angiotensin-Converting Enzyme Inhibitors↗