Development of a model based on body composition to predict drug kinetics; II. Application of the model to the use of digoxin in elderlies.

The applicability of a kinetic model for the prediction of steady-state blood levels, based on body composition as assessed by bioelectric impedance analysis (BIA), was applied to a population of elderly patients, candidates for digoxin therapy. Elderlies, all >70 years of age, underwent standard laboratory and clinical evaluation but no further characterization of liver or renal function. These 72 patients were given 0.125 mg digoxin for 5 days, in order to reach steady-state levels. Treatment was then interrupted and samples were collected 2 and 48 h after the last administration. Plasma digoxin levels were determined both by the immunochemical method with TDX and according to the BIA method described in the accompanying paper. Plasma levels calculated and measured in 2 h samples did not differ statistically, but levels were about 15% higher in the directly measured samples. There was a similar underestimation, i.e. about 15%, for the 48 h calculated levels. However, only approximately 5% of the levels were outside of the 95% confidence intervals as determined from the directly measured levels. These findings indicate that digoxin levels, calculated based on a BIA evaluation, may be sufficiently reliable, in the majority of patients, to allow direct determination of the more appropriate doses of digoxin.

Albuminuria and transferrinuria in essential hypertension. Effects of antihypertensive therapy.

The objectives of this study were to evaluate the effects of an ACE inhibitor (fosinopril) and a calcium antagonist (amlodipine) on the urinary albumin and transferrin excretion and their relationship to the blood pressure in essential hypertension. Twenty-four never-treated patients (mean age, 46.4 +/- 8.9 years) with a diastolic blood pressure between 90 and 114 mm Hg and normal renal function, randomly received amlodipine or fosinopril and, if the diastolic blood pressure was not normalized, doxazosin was added to the therapy. Twenty-four-hour ambulatory blood pressure monitoring and 24-h urine collection for albumin and transferrin measurements were performed before and after 3 and 6 months of therapy. Diastolic blood pressure was normalized in 23 patients (96%). Before treatment, microalbuminuria was present in 50% of patients. In the amlodipine and fosinopril group, antihypertensive therapy significantly decreased blood pressure and, only in the fosinopril group, albuminuria. Transferrinuria did not change significantly in both groups. Fosinopril lowered albuminuria in all patients, whereas amlodipine only in half of patients. Albuminuria, but not transferrinuria, was significantly correlated to the ambulatory blood pressure. This correlation was more pronounced for systolic than for diastolic pressure. In essential hypertensive patients with normal renal function, a high prevalence of microalbuminuria can be observed. Albuminuria appears to correlate with ambulatory blood pressure, particularly with systolic pressure. Intrarenal hemodynamic changes seem to play a more important role than systemic blood pressure decrease in the reduction of albuminuria. Transferrinuria does not seem a useful marker to follow-up nondiabetic hypertensive patients with early signs of glomerular dysfunction.

[The possible effects of galactosaminoglucuronoglycan sulfate on blood coagulation processes]. / Studio delle eventuali influenze del galattosaminglucuronoglicano solfato sui processi emocoagulativi.

Ten patients with osteoarthritis were treated in an open study with galactosaminoglucuronoglycan sulphate for 60 days (800 mg b.i.d. per os). The following haemostatic indices were measured before and after treatment: platelet count, adhesion and aggregation; prothrombin time and activity; partial thromboplastin time and antithrombin III. Total and HDL cholesterolemia, triglycerides, arterial pressure and heart rate were also measured. No blood coagulation index was found to be significantly altered in treated patients. In addition, neither variations from the normal limits of lipidemic and cardiocirculatory values nor adverse effects related to treatment were reported. Although the study was carried out in a limited population, these findings show that GGG does not interfere with the coagulation process and, from a more general point of view, they confirm its excellent tolerance.

[Heparan sulfate: its kinetic effects on fibrinolytic-coagulative parameters after oral administration]. / Eparansolfato: cinetica degli effetti su parametri fibrinolitico-coagulativi dopo somministrazione orale.

The effects of the oral administration of 100 or 200 mg of heparan sulphate or placebo over time were assessed in nine healthy volunteers. Blood samples were collected at 1, 2, 4, 6, 8 and 12 hours after administration to assay prothrombin activity, partially activated thromboplastin time, and the activation to tPA and PAI-1. A significant increase (P < 0.001) of tPA activity and a reduced inhibition of fibrinolytic systems by PAI-1 were observed. These effects, which were clearly dose-dependent, appeared 2 hours after administration and persisted for 6-8 hours. On the contrary, no changes were recorded in coagulative tests at the doses used.

[Heparan sulfate: efficacy and safety in patients with chronic venous insufficiency]. / Eparansolfato: efficacia e tollerabilità in pazienti affetti da insufficienza venosa cronica.

Fifty patients suffering from chronic venous disease were treated for 30 days with heparan sulphate 100 mg per os, b.i.d., or mesoglycan 50 mg per os, t.i.d., in a single blind random study. Both therapies led to a marked improvement in comparison to basal clinical values, but patients treated with heparan sulphate showed the greatest and most rapid regression of symptoms, associated with a significant improvement in plethysmographic index of capacitance and venous flow. Patients treated with heparan sulphate also showed an increased fibrinolytic activity and a reduced antithrombin III consumption, both of which were statistically significant.

A new low molecular weight heparin in the treatment of peripheral arterial disease.

A double blind study was conducted on patients afflicted with obstructive arteriopathy of the lower limbs in order to verify the efficacy and tolerability, in long term treatment, of a new low molecular weight heparin (Alfa LMW1). Of the 55 patients studied, 28 were treated with Alfa LMW1 given subcutaneously in doses of 8,000 I.U. AXa daily for 6 months; the remainder 27 were treated with Placebo. Efficacy of Alfa LMW1 was evaluated by monitoring the lower limb segmental pressures and some pressure ratios (thigh/arm, ankle/arm). Moreover, by means of the treadmill test, also checked were: time of claudication; ankle/arm pressure ratio before and after exercise and time required to return to initial pressure. By means of the strain gauge plethysmography, basal flow and peak flow after ischemia were also evaluated. The results obtained indicated a significant difference in efficacy between the two therapies, most notable after the third month. While in the Alfa LMW1 group a significant (p less than 0.01) and progressive improvement by the third month of treatment was seen, in the Placebo group a slight improvement was registered only at the end of the study and this was significantly inferior with respect to the comparison group.

Clinical and immunological evaluation of oral ribavirin administration in recurrent herpes simplex infections.

A total of 38 out-patients with recurrent oral or genital Herpes simplex virus infections received either oral ribavirin (800-1600 mg/day for 7 days) or placebo following a randomized and balanced protocol. Clinical and laboratory parameters, including haematological, metabolic and immunological tests, were checked in order to estimate tolerance to and efficacy of ribavirin on recurrent Herpes simplex virus infection and on the number of recurrences during the 12 months following treatment. Ribavirin showed definite superiority in the treatment of recurrent Herpes simplex virus 1, when compared to placebo, its efficacy being enhanced if treatment is started as soon as possible after infection has started. No significant modification of the parameters used to assess tolerance was noted; moreover there was no modification of the immunological parameters evaluated.