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Prolonged heparin administration during clopidogrel treatment in healthy subjects
H Caplain1, G D'Honneur, R Cariou
1Institut Aster, Hôpital Cognacq-Jay, Paris, France.
Insights
This study found no significant drug interactions between clopidogrel and heparin. Co-administration of these medications did not alter heparin consumption or affect bleeding times and platelet aggregation.
Area of Science:
- Pharmacology
- Clinical Pharmacology
Background:
- Clopidogrel is an antiplatelet medication.
- Heparin is an anticoagulant medication.
- Potential interactions between clopidogrel and heparin require investigation.
Purpose of the Study:
- To assess potential pharmacological interactions between clopidogrel and heparin.
- To evaluate the effect of clopidogrel on heparin's anticoagulant activity.
- To determine if co-administration alters bleeding time or platelet aggregation.
Main Methods:
- Randomized, placebo-controlled study in 12 healthy male subjects.
- Clopidogrel (75 mg daily) or placebo administered for 12 days.
- Sodium heparin infused to maintain activated partial thromboplastin time (APTT) ratio between 1.7-2.3.
Main Results:
- No statistically significant difference in APTT ratio between clopidogrel and placebo groups.
- Heparin consumption and bleeding times were not significantly altered by clopidogrel.
- Clopidogrel inhibited ADP-induced platelet aggregation; no further change with heparin co-administration.
Conclusions:
- No significant pharmacokinetic or pharmacodynamic interactions observed between clopidogrel and heparin.
- Co-administration of clopidogrel and heparin appears safe under the studied conditions.
- Further research may be warranted in specific patient populations.
Abstract:
The potential pharmacological interaction between clopidogrel and heparin was assessed in a randomized, placebo-controlled study carried out in 12 healthy male subjects. Clopidogrel 75 mg once daily or placebo was given in a randomized fashion for 12 days during two periods separated by a 21-day washout period. Sodium heparin was administered as a prolonged intravenous infusion at a starting dose of 300 IU/kg/24 hours then adjusted so as to maintain the activated partial thromboplastin time (APTT) ratio for subject versus control within the therapeutic range of 1.7 to 2.3 for 4 days from day 9 through day 13 of each period. For each period, the following main parameters were measured: total heparin consumption; APTT on days 1 and 8 to 12 before drug intake and on days 13, 14 and 26; bleeding time and platelet aggregation induced by 5 microM ADP on days 1, 8 to 10 and 12 before drug intake, and on days 14 and 26; APTT measured 3 times on day 9, i.e., before the start of heparin infusion, then 3 and 6 hours later. During day 9 to 13 period, the subject/control APTT ratio remained within the specified 1.7 to 2.3 range with no statistically significant difference between the clopidogrel and placebo treatments. The mean (+/-s.e.m.) volumes of heparin infused in each group were 81384+/-2793 IU and 79867+/-2788 IU in the clopidogrel and placebo groups, respectively. The 90% confidence interval of the mean heparin volume difference fell within the+/-10% interval of the placebo mean centered on zero. Bleeding time in the placebo group remained practically unchanged throughout the study. In the clopidogrel group, bleeding time prolongation factor was significantly increased from baseline to day 9, with clopidogrel alone then remained stable at 1.2 following co-administration of heparin until the end of treatment; hence, it was not modified by the coadministration of heparin. ADP (5 microM)-induced platelet aggregation was inhibited by 27+/-12% after 7 days of clopidogrel administration alone, and no significant further change was observed when heparin was coadministered. There were no adverse events that could be related to clopidogrel. In conclusion, under the study conditions, no interactions between clopidogrel and heparin were observed.