Interaction Study between Org 10172, a Low Molecular Weight Heparinoid, and Acetylsalicylic Acid in Healthy Male Volunteers

Boer, A. de; Danhof, Meindert; Cohen, Adam F.; Magnani, H N; Breimer, D. D.

doi:10.1055/s-0038-1646390

Cited by 6 publications

(10 citation statements)

References 17 publications

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“…In contrast to our results, de Boer et al. [8] observed markedly prolonged bleeding times after 2 × 500 mg ASA alone (14 min) and the combined treatment with Org 10172 15 min after injection (20 min). Bleeding time tended to be more prolonged after the combination.…”

Section: Discussioncontrasting

confidence: 99%

“…We found that the inhibiting effect of ASA on platelet function as evaluated by collagen induced platelet aggregation was unaffected by reviparin, since aggregation after combined treatment was not different from ASA alone. Conflicting data have been reported by other investigators [7, 8, 21]. De Boer et al.…”

Section: Discussionmentioning

confidence: 96%

“…Prolongation of bleeding time after ASA or heparins alone has been reported inconsistently [7, 8, 18]. There are several reports of possible interaction between ASA and heparins.…”

Section: Discussionmentioning

confidence: 99%

“…De Boer et al. [8] found that inhibiting effects of ASA on platelet function were not influenced by the LMW heparinoid Org 10172. Mean E C 50 values for collagen induced platelet aggregation during combined treatment with ASA + Org 10172 averaged 3.4 ng ml −1 collagen and were not statistically different from values during ASA treatment alone (3.75 ng ml −1 ) 90 min after injection.…”

Section: Discussionmentioning

confidence: 99%

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Interaction between the LMWH reviparin and aspirin in healthy volunteers

Klinkhardt

Breddin

Esslinger³

et al. 2000

Brit J Clinical Pharma

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Aims To investigate potential interactions between reviparin and acetylsalicylic acid (ASA 300 mg o.d. from day 1±5).Methods In an open, randomized, three-way-cross over study nine healthy volunteers received reviparin (s.c. injection of 6300 anti-Xa units) or placebo from days 3 to 5 and acetylsalicylic acid (ASA 300 mg) or placebo from days 1 to 5. Assessments included bleeding time (BT), collagen (1 mg ml x1 ) induced platelet aggregation (CAG), heptest, plasma antifactor Xa-activity and activated partial thromboplastin time (aPTT). Results Median bleeding time at day 5 was 5.5 min after reverparin alone and after ASA alone and was 9.6 min after the combination of reviparin and ASA. ASA treatment reduced CAG from 84% to 40 to 50% of A max ; values after combined treatment of reviparin with ASA were not different from those after ASA alone. aPTT was prolonged to 32 s after reviparin; this effect was not modi®ed if subjects received ASA. Combined treatment with ASA and reviparin had no effect on plasma anti-Xaactivity and heptest compared with reviparin alone. Conclusions We could not entirely exclude a small interaction between reviparin and ASA on bleeding time, but the effect is probably without clinical signi®cance.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 96%

“…Prolongation of bleeding time after ASA or heparins alone has been reported inconsistently [7, 8, 18]. There are several reports of possible interaction between ASA and heparins.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Interaction between the LMWH reviparin and aspirin in healthy volunteers

Klinkhardt

Breddin

Esslinger³

et al. 2000

Brit J Clinical Pharma

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“…Combined administration of reviparin and ASA increased median BT from 5.4 minutes at day 1 to 9.6 minutes at day 5 with a p value of less than 0.01 and, compared to reviparin plus oral placebo (median BT 5.1 and 5.5 minutes at days 1 and 5, respectively) with a p value of less than 0.05. De Boer and associates (30) studied the effect of the LMWH agent ORG10172 (IV bolus of 325 aXa U followed by 750 U twice daily) and 2 doses of 500 mg ASA. The effect of ASA on BT was highly variable and more pronounced when the combination of the 2 drugs was given.…”

Section: Asa Plus Heparin and Bleedingmentioning

confidence: 99%

Effects of PEG-Hirudin in Clotting Parameters and Platelet Function and its Interaction with Aspirin in Healthy Volunteers

Esslinger¹,

Köhne

Radziwon³

et al. 2003

Clin Appl Thromb Hemost

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The purpose of this study was to investigate the pharmacodynamics of PEG-Hirudin and its potential interactions with acetylsalicylic acid (ASA 325 mg once daily from days 1-3). In a randomized, 2-way cross-over trial, 6 healthy volunteers received PEG-Hirudin (i.v. bolus of 0.2 mg/kg + 0.02 mg/kg/h for 24 hours) and placebo (i.v. bolus + 24-hour infusion). In a further randomized, 3-way cross-over trial another 9 healthy volunteers received ASA (325 mg) or oral placebo from days 1 to 3 and PEG-Hirudin (0.2 mg/kg + 0.02 mg/kg/h for 24 h) or i.v. placebo on day 3. Assessments included bleeding time (BT), collagen (1 microgram ml(-1))-induced platelet aggregation (CIPA), platelet adhesion, ecarin clotting time (ECT), activated clotting time (ACT), plasma anti-factor IIa activity (aIIa), and activated partial thromboplastin time (aPTT). Ten minutes after the PEG-Hirudin injection/starting the infusion, mean plasma concentration was 3.1 microgram/mL and aPTT, ECT, and ACT were prolonged up to 80, 309, and 233 seconds, respectively. During the last 8 hours of the 24-hour infusion mean PEG-Hirudin plasma concentration was 1.3 microgram/mL. In the interaction study, ASA significantly inhibited CIPA. At 6 hours after administration, on day 3 mean BT was 6.5 minutes after PEG-Hirudin alone, 18.2 minutes after ASA alone, and 32.9 minutes after combined administration of ASA and PEG-Hirudin. PEG-Hirudin (0.2 mg/kg + 0.02 mg/kg/h for 24 hours) administered alone or together with 325 mg ASA proved to be safe in healthy volunteers. Combined use of PEG-Hirudin and ASA significantly increased the mean bleeding time compared to ASA or PEG-Hirudin monodrug administration. None of the clotting parameters or platelet function tests correlated with the prolongation of the bleeding time.

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Anticoagulant and anti-platelet effects are maintained following coadministration of otamixaban, a direct factor Xa inhibitor, and acetylsalicylic acid

Hinder

Frick²,

Rosenburg³

et al. 2006

Thromb Haemost

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The pharmacokinetics, pharmacodynamics and safety of the direct factor Xa inhibitor, otamixaban, with and without concomitant acetylsalicylic acid (ASA) were investigated in healthy volunteers. The study was a double-blind, placebo-controlled 3-way crossover study. Sixty-eight male volunteers in total were randomised to otamixaban, ASA, or otamixaban with ASA. ASA (300 mg once a day) was started 2 days before and continued on the day of the otamixaban 6-hour IV infusion (0.3 and 0.5 mg/kg). Pharmacokinetic and pharmacodynamic parameters (coagulation markers, platelet function tests and skin bleeding time) were determined. Drug interaction was assessed by the ratios of geometric means and 90% confidence intervals (90% CI)of the parameter estimates. Pharmacokinetic parameters of otamixaban remained unchanged with ASA. Ratios of geometric means (90% CI) were for Ceoi 96.54 (91.21-102.19) and 95.04 (90.10-100.24) and for AUC 98.0 (93.92-102.25) and 95.90 (92.61-99.31), for 0.3 and 0.5 mg/kg, respectively. No drug interaction was observed between otamixaban and ASA on the coagulation and platelet function parameters. Neither otamixaban nor ASA had an effect on skin bleeding time; their co-administration led to a slight prolongation of skin bleeding time above the normal range without any clinically relevant bleeding. This study demonstrated that the desired effects of otamixaban and ASA, namely anticoagulation and platelet inhibition, respectively, are maintained during co-administration of both drugs.

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Interaction Study between Org 10172, a Low Molecular Weight Heparinoid, and Acetylsalicylic Acid in Healthy Male Volunteers

Cited by 6 publications

References 17 publications

Interaction between the LMWH reviparin and aspirin in healthy volunteers

Interaction between the LMWH reviparin and aspirin in healthy volunteers

Effects of PEG-Hirudin in Clotting Parameters and Platelet Function and its Interaction with Aspirin in Healthy Volunteers

Anticoagulant and anti-platelet effects are maintained following coadministration of otamixaban, a direct factor Xa inhibitor, and acetylsalicylic acid

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