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Biomedical subjects

G Bianchetti

Publications and source records attributed to G Bianchetti.

82 records · Page 5Linked to original sources

Gas chromatographic method for the determination of nomifensine in human plasma.

An analytical method based on solvent extraction, formation of a fluorinated derivative and quantitation by gas-liquid chromatography using an electron capture detector has been developed for the determination of nomifensine in biological fluids. The specificity (controlled by mass spectrometry) and the sensitivity appear to be satisfactory for drug level measurements in human body fluids. Its relative simplicity in fact permits its use in serial analysis.

Antidepressive Agents↗

Positive chronotropic effect of dialysable peptides derived from plasmin digestion of bovine fibrinogen preparations.

Low-molecular weight dialysable peptides, obtained by plasmin degradation of purified bovine fibrinogen preparations, have been shown to increase the chronotropic activity of isolated rat atria. This effect was dose dependent and was inhibited by inhibitors of glycolysis (NaF and 2-deoxy-D-glucose), but not by an inhibitor of oxidative phosphorylation (2, 4-dinitrophenol). Propranolol, a beta-blocking agent, was also ineffective. Fibrinogen-derived peptides increased both cAMP levels and phosphorylase alpha activity in stimulated atria. The increase of these parameters was transitory and appeared to precede the occurrence of the positive chronotropic effect. In the test situation used, the biochemical and functional modifications induced by fibrinogen-derived peptides were similar to those induced by glucagon.

Animals↗

Pharmacokinetics and effects of propranolol in terminal uraemic patients and in patients undergoing regular dialysis treatment.

Propranolol blood and plasma levels were measured after a single oral dose of 40 mg in patients with chronic renal failure, in patients undergoing regular dialysis treatment, and in healthy volunteers. Peak levels were observed in all cases within 1.5 to 3 hours. However, peak blood and plasma concentrations of propranolol in the chronic renal failure group were 2- to 3-fold higher (161 +/- 41 ng/ml) than those observed in the dialysis patients (47 +/- 9 ng/ml) and in the healthy volunteers (26 +/- 1 ng/ml). The apparent plasma clearance was also significantly reduced in the patients with chronic renal failure. The data suggest a reduced hepatic extraction in chronic renal failure patients. A significant increase in the fraction of the dose available to the systemic circulation was also found, together with a modification of apparent plasma half-life and volume of distribution in regular dialysis patients during the dialysis day as compared with the after-dialysis day. No extraction of propranolol by the dialyzer was noticed. Marked fluctuations in propranolol blood concentrations were also observed in patients on regular dialysis following continuous propranolol treatment. The suppressive effect of propranolol on plasma renin activity did not fully correlate with the hypotensive effect of the drug. On the basis of the reported data, propranolol should be used with great caution and at low doses in chronic renal failure.

Adult↗

Pharmacokinetics of nomifensine in man.

Nomifensine pharmacokinetics were determined in healthy volunteers after the oral administration of 50 mg of the drug. Peak plasma levels of 95-177 ng/ml were attained within 1 to 4 hrs, and the apparent plasma half-lives ranged from 3.3 to 4.9 hrs. Assuming 100% bioavailability the drug has a relatively large apparent volume of distribution. From these findings it appears that the pharmacokinetics profile of nomifensine is considerably different from those of other known antidepressants. Implications for dosages schedules are discussed.

Administration, Oral↗

Hypotensive and renin-suppressing activities of propranolol in hypertensive patients.

1. In patients with mild or moderate essential hypertension, oral propranolol, given in incremental doses, produced a moderate but significant lowering of blood pressure which was correlated with the concentration of propranolol in plasma. 2. Propranolol also reduced plasma renin activity (PRA) in the supine posture, on standing and after intravenous frusemide. However, 'supine' and 'frusemide' PRA values were markedly reduced at a plasma concentration of propranolol that had little effect on blood pressure. 3. On administration of propranolol there was little correlation between blood pressure decrease and PRA suppression, and even less between pretreatment PRA values and hypotensive response. 4. It is concluded that in patients with mild and moderate hypertension and low or normal plasma renin activity, suppression of PRA is not an important determinant of the hypotensive response to propranolol.

Administration, Oral↗

Studies of the absorption and removal of propranolol in hypertensive patients during therapy.

The variability of plasma propranolol concentrations has been determined in a large group of patients being treated with the drug. Although the average patient achieved a therapeutic plasma level with 160 mg/day, there was marked interpatient variation. This was found to be primarily the result of differences in effective absorption of the drug, which averaged 46% of the oral dose but ranged from 20 to 80%. Propranolol disappeared from plasma with a half-life of 4.7 hours and its removal appeared to follow dose independent kinetics with no evidence of saturation of hepatic metabolism. The derived pharmacokinetic values of volume of distribution and clearance rate have been used to provide guidelines for initiating propranolol therapy intravenously, and the schedule of 8 mg as a loading dose and 0.02 mg/min as a sustaining dose has been suggested.

Administration, Oral↗

Pharmacokinetic interactions of progabide with other antiepileptic drugs.

The influence of progabide, a new antiepileptic drug, on the pharmacokinetic profiles of phenobarbital, phenytoin, carbamazepine, and valproic acid was evaluated in four separate studies, each including six young healthy volunteers. The pharmacokinetic parameters of the associated antiepileptic drugs were measured before and after repeated administration of progabide (600 mg t.i.d.) for 15 days. A significant reduction of the total body clearance of both phenytoin and phenobarbital and a higher Cmax value of carbamazepine epoxide and phenobarbital were observed. No modifications were noticed for the kinetic profiles of carbamazepine and valproic acid. These modifications may be of clinical relevance and suggest that, as a general rule, when progabide is added to an established treatment with phenobarbital or phenytoin or carbamazepine, an adjustment of previous posology may be necessary.

Adult↗

[Acute diltiazem poisoning: kinetic and hemodynamics study].

The authors report three cases of diltiazem overdose with hypotension and atrio-ventricular conduction disturbances. Hemodynamic study in 2 cases showed a hyperkinetic state with a decrease of systemic vascular resistances. Diltiazem kinetics studied in 2 cases showed a plasma half life of 5.4 and 8.3 hours, a prolonged absorption until the 28th hours in one case. Treatment included gastric lavage, oral activated charcoal (2 cases), plasma expanders and in 2 cases vasopressors with alpha effects. All three patients recovered.

Acute Disease↗

[Patent ductus arteriosus in premature newborns. Treatment with indomethacin (author's transl)].

The pharmacokinetic and pharmacodynamic effects of indomethacin were studied in 18 prematures with patent ductus arteriosus, treated either enterally (group I, n = 7), or intravenously (group II, n = 11). A definitive closure assessed by echocardiography was observed in 13 cases (72%), and it was only transient in 4 cases (21%). Assisted ventilation was discontinued between 1 and 6 days following therapy in 14 cases. In most cases, indomethacin induced a significant reduction of diuresis but the plasma creatinine level increased above 15 mg/l in 3 cases only. The elimination half life of indomethacin (t 1/2 beta), of 40.3 +/- 12.2 hours in group I and 33.9 +/- 11.7 hours in group II, is increased as compared with adults. The difference of the surface under the curve (AUC O leads to 24 h, ng.ml-1.h-1) between the infants who presented complete or transient closure, suggests a relationship between the biodisponibility of the drug and the effect on patent ductus arteriosus. Treatment with indomethacin is an interesting alternative to surgical ligation in prematures with patent ductus arteriosus. Because of its side effects, especially on the kidneys, it is recommended to use this treatment only in intensive care units. The intravenous route seems to be better than the enteral route.

Administration, Oral↗