study to assess bemiparin pharmacokinetics in renal insufficiency and in the elderly

Conditions: Renal Insufficiency

Summary: 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.


Eligibility criteria:
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 \ 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 \ 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

Keywords: renal insufficency low molecular weight heparin pharmacokinetics elderly