Study to Assess Bemiparin Pharmacokinetics in Renal Insufficiency and in the Elderly
Study to Assess Bemiparin Pharmacokinetics in Renal Insufficiency and in the Elderly
Open pharmacokinetic study with 5 parallel groups and two treatment phases (bemiparin 3,500
 IU multiple dose and bemiparin 115 IU/kg single dose). The bemiparin pharmacokinetic profile
 will be assessed by measuring its effects on the coagulation cascade. Plasma anti-Xa activity
 (measured using chromogenic amidolytic assay) in IU per milliliter will be the primary
 endpoint to assess the pharmacokinetic profile of bemiparin.
Inclusion Criteria:

 Non-elderly healthy volunteers (Group I):

 -  Male or female subjects aged between 18 and 65 years

 -  body weight, clinical history, physical examination, vital signs (systolic and
 diastolic blood pressure, heart beat rate and body temperature), ECG and laboratory
 tests (hemogram and biochemistry) within normal range

 -  without evidence of significant organic or psychiatric illness

 -  who have accepted to participate in the study and have signed the written informed
 consent.

 Patients with renal insufficiency (Groups II, III and IV):

 -  Male or female subjects aged between 18 and 65 years, who will be assigned to one of
 the following groups according to renal function:

 -  Group II: mild renal insufficiency (creatinine clearance > 50 to 80 ml/min);

 -  Group III: Moderate renal insufficiency (creatinine clearance: 30 to 50 ml/min);

 -  Group IV: Severe renal insufficiency (creatinine clearance < 30 ml/min). The
 degree of renal insufficiency will be calculated on the basis of determination of
 creatinine clearance measuring total urinary output over a 24-h period and serum
 creatinine levels. Urine samples will be collected no more than 2 weeks before
 the first experimental period.

 -  Patients with renal insufficiency must have a stable renal function during the 3
 months before their inclusion in the study.

 -  They must have a body weight between 45 and 110 Kg.

 -  They have to accept to participate in the study and have signed the written informed
 consent.

 Elderly healthy volunteers (Group V):

 -  Male or female subjects aged > 65 years old who fulfill with the remaining inclusion
 criteria specified for non-elderly healthy volunteers.

 Exclusion Criteria:

 Non-elderly healthy volunteers (Group I):

 -  Previous history of alcoholism or drugs consumption

 -  Important consumer of exciting drinks

 -  Hypersensitivity, allergy, idiosyncrasy to medicines

 -  Taking another medication four weeks before the initiation of the trial including
 medication without prescription and medicinal plants

 -  Positive serology of hepatitis B, C or HIV virus

 -  History or clinic evidence of concomitant disease

 -  Familiar history of coagulation's disorders

 -  surgery within the previous 6 months

 -  Women who are pregnant or who are not using effective contra conceptive methods

 -  Ethanol, cannabis, cocaine, amphetamine, benzodiazepin or opiate in urine

 -  Current platelet count < 100.000/mm3 or serum K > 5,5 mEq/L

 -  Any contraindication to bemiparin administration in order to authorized summary
 product characteristics

 -  Healthy volunteers who are not participating in another clinical trial or have not
 done so in the past 2 months

 -  To give blood in the four weeks before beginning of the trial

 Patients with renal insufficiency or elderly healthy volunteers (Groups II, III, IV, V):

 -  Previous history of alcoholism or drugs consumption

 -  Important consumer of exciting drinks

 -  Hypersensitivity, allergy, idiosyncrasy to medicines

 -  Treatment with enzymatic inhibitors or inductors medicines

 -  Administration with ASA of dosis > 125 mg/day and/or NDAIs with half-life > 20 hours
 or with high antiagregant effect during the previous ten days to the inclusion

 -  Chronic hepatopatology

 -  bilirubin levels > 1,5 mg/dl and/or increment of AST/ALT levels twice higher than
 maximum limit of normality

 -  prothrombin time 20% higher than maximun limit of normality and haemoglobine < 8gr/dl
 or albumim levels <3gr/dl

 -  Previous history of acute infarction of myocardium, cardiac ischemic or arrhythmia

 -  Acute illness in the previous week to the participation

 -  Familiar history of coagulation's disorders

 -  surgery within the previous 6 months

 -  Women who are pregnant or who are not using effective contra conceptive methods

 -  Ethanol, cannabis, cocaine, amphetamine, benzodiazepin or opiate in urine

 -  Current platelet count < 75.000/mm3 or serum K > 6 mEq/L

 -  Any contraindication to bemiparin administration in order to authorized summary
 product characteristics

 -  Healthy volunteers who are not participating in another clinical trial or have not
 done so in the past 2 months

 -  To give blood in the four weeks before beginning of the trial

 -  Subjects in haemodialysis or peritoneal dialysis