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M Amouretti

Publications and source records attributed to M Amouretti.

90 records · Page 5Linked to original sources
PubMedDate not supplied

Pharmacokinetics of milnacipran in liver impairment.

The pharmacokinetics of single 50 mg oral and intravenous doses of milnacipran, a new non tricyclic antidepressant drug, were compared in 11 chronic liver impaired (LI) subjects and in 6 control subjects. Hepatic impairments, classified according to the PUGH scale were moderate (1 grade A), intermediate (6 grade B) and severe (4 grade C). Concentrations of unchanged drug and its conjugated form (its main metabolite) were measured in plasma and urines. In control subjects, milnacipran present high absolute bioavailability (mean value of 90%). Around 50% of the dose are excreted in urines as unchanged, while around 14% are excreted as glucuroconjugate. The remaining is composed of free and conjugated phase I inactive metabolites. Administration of milnacipran in LI subjects results in non significant changes in its pharmacokinetics, although its variability is increased. Unchanged drug exposure is not modified in LI subjects, while plasma levels of the conjugate are slightly decreased compared to the control group. This could either be due to a slight reduction in the conjugation process, or to a change in the distribution of the drug as urine excretion of both unchanged and conjugated forms are not modified compared to the control group. A few LI subjects present supra-bioavailability resulting in higher drug exposure after oral administration than after intravenous infusion. These modifications are not clinically relevant as drug exposure of the parent drug is not modified. As the unchanged drug is the only compound responsible for the activity of milnacipran, no dosage adjustment is needed in patients presenting liver impairment.

Administration, Oral↗
PubMedDate not supplied

[Intra-hepatic post-traumatic cholestasis. Apropos of 22 cases].

The authors report 22 observations of patients showing an intra-hepatic cholestasis following a traumatism. The frequency of this complication amounted to about 1.5 p. 100. Among the mechanisms of this cholestasis some factors were kept in mind: 1. the severity of the traumatism; 2. the surgical act; 3. the use of massive transfusions, the polyvisceral complications of the traumatic shock, the infectious complications. The pathophysiology of this cholestasis seems to be in relation to an increase of the production of the conjugated bilirubin. This production is associated with a decrease of the biliary excretion depending essentially on hepatic intracellular injury, secondary to: the hemorragic shock, the anoxia, the surgical intervention, the infection. From these different factors, they draw practical conclusions as much in the diagnosis of cholestasis as in the therapeutics.

Adult↗