mab: the incidence of the composite primary endpoint (death, MI, or uTVR at 30 days) showed that abciximab was significantly more effective on clinically relevant endpoints, with 7.6% in the Aggrastat and 6.0% in the abciximab group (p=0.038), which was mainly due to a significant increase in the incidence of MI at 30 days (respectively 6.9% vs. 5.4%; p=0.04).
5.2 Pharmacokinetic properties
Distribution
Tirofiban is not strongly bound to plasma protein, and protein binding is concentration-independent in the range of 0.01–25 microgram/ml. The unbound fraction in human plasma is 35%.
The distribution volume of tirofiban in the steady state is about 30 litres.
Biotransformation
Experiments with 14C-labelled tirofiban showed the radioactivity in urine and faeces to be emitted chiefly by unchanged tirofiban. The radioactivity in circulating plasma originates mainly from unchanged tirofiban (up to 10 hours after administration). These data suggested limited metabolisation of tirofiban.
Elimination
After intravenous administration of 14C-labelled tirofiban to healthy subjects, 66% of the radioactivity was recovered in the urine, 23% in the faeces. The total recovery of radioactivity was 91%. Renal and biliary excretion contribute significantly to the elimination of tirofiban.
In healthy subjects the plasma clearance of tirofiban is about 250 ml/min. Renal clearance is 39–69% of plasma clearance. The half-life is about 1.5 hours.
Gender
The plasma clearance of tirofiban in patients with coronary heart disease is similar in men and women.
Elderly patients
The plasma clearance of tirofiban is about 25% less in elderly (>65 years) patients with coronary heart disease in comparison to younger (≤65 years) patients.
Ethnic groups
No difference was found in the plasma clearance between patients of different ethnic groups.
Coronary Artery Disease
In patients with unstable angina pectoris or NQWMI the plasma clearance was about 200 ml/min, the renal clearance 39% of the plasma clearance. The half-life is about two hours.
Impaired renal function
In clinical studies, patients with decreased renal function showed a reduced plasma clearance of tirofiban depending on the degree of impairment of creatinine clearance. In patients with a creatinine clearance of less than 30 ml/min, including haemodialysis patients, the plasma clearance of tirofiban is reduced to a clinically relevant extent (over 50%) (see section 4.2). Tirofiban is removed by haemodialysis.
Liver failure
There is no evidence of a clinically significant reduction of the plasma clearance of tirofiban in patients with mild to moderate liver failure. No data are available on patients with severe liver failure.
Effects of other drugs
The plasma clearance of tirofiban in patients receiving one of the following drugs was compared to that in patients not receiving that drug in a sub-set of patients (n=762) in the PRISM study. There were no substantial (>15%) effects of these drugs on the plasma clearance of tirofiban: acebutolol, alprazolam, amlodipine, aspirin preparations, atenolol, bromazepam, captopril, diazepam, digoxin, diltiazem, docusate sodium, enalapril, furosemide, glibenclamide, unfractionated heparin, insulin, isosorbide, lorazepam, lovastatin, metoclopramide, metoprolol, morphine, nifedipine, nitrate preparations, oxazepam, paracetamol, potassium chloride, pr
