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M Buraglio

Publications and source records attributed to M Buraglio.

9 recordsLinked to original sources
PubMed2002

A 3-way crossover study to evaluate the pharmacokinetic interaction between nateglinide and diclofenac in healthy volunteers.

OBJECTIVE: To assess in healthy male volunteers (n = 18) the effect of diclofenac, a non-steroidal anti-inflammatory analgesic drug used for treatment of rheumatic diseases, on the pharmacokinetics of nateglinide, a new oral hypoglycemic agent that acts by a novel therapeutic mechanism to stimulate insulin release. The effects of nateglinide on the pharmacokinetics of diclofenac were also investigated. METHODS: This open-label study was conducted as a randomized, 3-period, 6-sequence, crossover investigation consisting of 2 reference treatment periods (diclofenac 75 mg or nateglinide 120 mg, alone) and 1 test period (concomitant nateglinide and diclofenac). On the days when nateglinide was administered, subjects received a 120 mg dose at the start of the study day and a second 120 mg dose 4 h after the first. A 2 to 7-day washout interval separated each of the study periods. Nateglinide and diclofenac plasma concentrations were determined up to 12 and 24 h, respectively. RESULTS: Administration of diclofenac did not alter the pharmacokinetics of nateglinide in healthy subjects. Similarly, concurrent administration of nateglinide with diclofenac did not alter the pharmacokinetics of diclofenac in these subjects. All treatments were considered to have been both safe and well tolerated. CONCLUSIONS: These data indicate that concomitant administration of diclofenac with nateglinide does not significantly alter the pharmacokinetic profile of either drug.

Adult↗
PubMed1998

Comparative pharmacokinetics and pharmacodynamics of recombinant human interferon beta-1a after intramuscular and subcutaneous administration.

The pharmacokinetics and pharmacodynamics of recombinant human interferon beta (IFN-beta-1a) were compared after intramuscular administration of two preparations (Rebif(R) and AvonexTM) and subcutaneous administration of Rebif(R). Healthy volunteers (n = 30) received a single dose (60 µg) of each of the three treatments in a randomised crossover study. Serum concentrations of IFN-beta were measured by enzyme-linked immunosorbent assay over 24 h after dosing. Pharmacodynamics were assessed by measurement of intracellular 2',5'-oligoadenylate synthetase activity, and serum neopterin and beta2-microglobulin concentrations, over 144 h after dosing. There was no significant difference between the three treatments in peak serum IFN-beta concentrations (Cmax) or area under the concentration-time curve (AUC). No significant differences in pharmacodynamic measures were observed between the three treatments. It is concluded that the bioavailability of IFN-beta-1a is equivalent after subcutaneous or intramuscular administration of Rebif(R), and intramuscular administration of AvonexTM. Copyright Rapid Science Ltd

Journal Article↗
PubMed1987

Congenital deficiency of alpha-2-adrenoceptors on human platelets: description of two cases.

The biochemistry and functionality of platelets from two related subjects (mother and son) with alpha-2-adrenoceptor-deficient platelets has been evaluated. Radioligand binding experiments with the specific alpha-2-adrenergic-receptor antagonist, 3H-yohimbine, showed a drastic reduction of alpha-2-adrenoceptors in platelets from both subjects in comparison with the control values. Electron microscopy studies revealed a normal morphology and a normal number of alpha granules and dense bodies. Levels of adenine nucleotides; 5-hydroxytryptamine; B-thromboglobulin; platelet-factor-4 and thromboxane A2 production were within normal limits. Platelet aggregation and 5-hydroxytryptamine production in response to adrenalin (at concentrations up to 50 microM) were absent, whereas ADP, AA, PAF, collagen and thrombin-induced aggregation, secretion, Ca++ flux and thromboxane A2 production were normal. The inhibitory effect caused by different concentrations of prostacyclin on Ca++ flux, aggregation, secretion and thromboxane A2 production of platelet functionally lacking of alpha-2-adrenoceptor was not distinguishable from control platelets and platelets preincubated with yohimbine.

Adult↗
PubMed1987

Absence of (-) [3H]desmethoxyverapamil binding sites on human platelets and lack of evidence for voltage-dependent calcium channels.

The two major pathways for Ca2+ entry into cells are potential-sensitive channels and receptor-operated channels. The main object of this investigation was to identify which mechanism regulates Ca2+ entry into human platelets. Platelet stimulation with thrombin, adenosine diphosphate, platelet activating factor and arachidonic acid resulted in a concentration-dependent 2.5-3-fold increase in cytoplasmic free calcium concentration over the basal levels (140 +/- 32 nM or 104 +/- 21 respectively) as measured with the fluorescent dyes Quin-2 and Fura-2. Adrenaline and collagen had no effect in promoting intracellular Ca2+ increase as measured with Quin-2 and little effect when measured with Fura-2. Incubation of Quin-2-loaded platelets with the calcium antagonists verapamil and diltiazem, which are known to inhibit Ca2+ entry from voltage-gated channels in many types of cells, over the concentration range 10(-8) - 10(-4) M did not alter significantly either the resting or the cytoplasmic free Ca2+ after stimulation of platelets by several agonists. Moreover, the calcium antagonists exhibited little or no effect on aggregation and 5-hydroxytryptamine secretion induced by platelet activating factor, adenosine diphosphate, collagen or arachidonic acid in whole blood, platelet-rich plasma or washed platelets when employed at concentration ranges as above. Similar results were obtained in washed thrombin-stimulated platelets. High doses of verapamil (but not diltiazem) inhibited platelet aggregation and secretion in response to adrenaline. Direct radioligand binding studies with (-)[3H]desmethoxyverapamil showed that platelet membranes have no receptors for this drug, suggesting that Ca2+ entry occurs in human platelets via a pathway different from potential-sensitive Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

[Antitubercular agents].

Author resume the most important stages of the antitubercular struggle. Then they consider the action mechanisms of single drugs, often not well known, such the action mechanism of pyrazinamide. At present, the criteria of effectiveness, tolerance, availability and economy allow to use rationally and not arbitrarily the antitubercular drugs and these criteria also assure the best therapeutic results.

Antimetabolites↗
PubMed1984

Changes of lymphocyte beta-adrenergic receptors after surgical stress.

In this study the authors' purpose was to observe the effects of surgical stress on the number of lymphocyte beta-adrenergic receptors in hypertensive and normotensive subjects. It was noticed that after surgery a significant reduction occurred in the number of binding sites of lymphocytes of both hypertensive and normotensive subjects. The time course of recovery to the pre-operative values of binding sites varied between the two groups, being slower in normotensive than in hypertensive patients. This might suggest a different pattern of regulation of the beta-adrenergic receptor between hypertensive and normotensive subjects.

Adult↗
PubMedDate not supplied

Safety, pharmacokinetics and pharmacodynamics of recombinant human tumour necrosis factor-binding protein-1 (Onercept) injected by intravenous, intramuscular and subcutaneous routes into healthy volunteers.

The safety, pharmacokinetics and pharmacodynamics of recombinant human tumour necrosis factor-binding protein-1 (r-hTBP-1, Onercept) were investigated after intravascular and extravascular injection, in three studies in healthy volunteers. Subjects received Onercept as single intravenous doses of 5, 15, 50 and 150 mg, or single IV, IM, SC injection of 50 mg, or six repeated SC injections of 50 mg. Based on vital signs, hematology and blood chemistry, antibodies to study drug and local tolerability, r-hTBP-1 exhibited a remarkably safe profile. There was no evidence of alteration of hepatic oxidative metabolism. Recombinant-hTBP-1 showed linear pharmacokinetics that could be described by a triexponential model, and exhibited an initial half-life of 30 min, an intermediate half-life of 4 hours and a terminal elimination half-life of about 15 hours, although it was prolonged to 21 hours after repeated SC injections. The total clearance was estimated at 4 l/h. The initial (Vc) and steady state (Vss) volumes of distribution were approximately 4 l and 10 l, respectively. Renal clearance was minimal, representing around 2.5% of the total clearance, and remained constant after increasing doses of r-hTBP-1. The absorption was slow and biphasic. The immunoactivity of r-hTBP-1 was closely related to its biological activity, although the assessment was limited to only some of the samples. As anticipated in normal healthy volunteers, the pharmacodynamic response was generally not different from placebo. Total TNF-alpha serum levels increased slightly, 1 hour following IV administration of 50 mg and 150 mg r-hTBP-1. However, no major increase in the active entity levels (free TNF-alpha) was observed. In addition, no TNF-alpha-driven biological response was observed, i.e. C-reactive protein, IL-6 and fibrinogen remained almost constant, as did transferrin and albumin. Its safety profile and pharmacokinetic characteristics make Onercept a candidate drug suitable for antagonising pathologically high levels of TNF-alpha as reported in inflammatory, immune and cardiovascular diseases.

Adult↗