Pharmacokineties and tissue distribution of 99mTc-labelled enoxaparin in the rat: evaluation of dosimetry parameters

Linhart, N; Laforest, M.D.; Guiraud-Vitaux, F.; Gardin, I.; Petiet, Alexandra; Berthelot, Jean-Michel; B, Bok

doi:10.1016/0753-3322(90)90135-v

Cited by 9 publications

(4 citation statements)

References 10 publications

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“…Dalteparin and certoparin exhib ited nearly the same A (3.0 ± 1.2 and 2.8 ± 0.4 U/mL), AUC (2.63 ± 0.67 and 2.52 ± 0.7 U •hr/mL), and tPC (61.3 ± 19.28 and 63.0 ± 14.5 mL/kg•hr) of the aXa activity. In the trials of Saivin et al 24 and Linhard et al, 23 comparable areas under the curves and total plasma clearances were described for nadroparin and enoxaparin. Comparing the pharmacodynamic data for the aXa activity of dalteparin and certoparin, the in vivo aXa properties were very similar, even though the two LMMHs have different in vitro activities and different molecular weights.…”

Section: Discussionmentioning

confidence: 82%

“…This is comparable to the findings of Aiach et al 8 The two LMMHs showed similar half lives of the aXa activities, we found a T ½ α of 32 ± 10 min and 28 ± 6 min and a T ½β of 80 ± 46 min and 73 ± 24 min for dal teparin and certoparin, respectively (Table 2). Fareed et al 22 found an aXa half-life of 70 min and Linhart et al 23 a half-life of 88 min after IV injection of LMMH (enoxaparin) in rats. Dalteparin and certoparin exhib ited nearly the same A (3.0 ± 1.2 and 2.8 ± 0.4 U/mL), AUC (2.63 ± 0.67 and 2.52 ± 0.7 U •hr/mL), and tPC (61.3 ± 19.28 and 63.0 ± 14.5 mL/kg•hr) of the aXa activity.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of the Pharmacodynamic and Pharmacokinetic Profiles of Two Low-Molecular-Mass Heparins in Rats

Piazolo

Harenberg²,

Malsch³

et al. 1997

Semin Thromb Hemost

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The pharmacodynamic and pharmacokinetic properties of certoparin and dalteparin were analyzed after intravenous and subcutaneous administration. The two different LMMHs exhibited different molecular mass and in vitro activities. The aim of the present study was to show the extent to which these in vitro differences influenced the biological activity and pharmacokinetics in vivo. It was possible to measure the plasma concentrations of the LMMHs by using a competitive assay with protamine-coated latex beads. Both LMMHs showed a biphasic aXa and aIIa activity curve after intravenous injection. Certoparin and dalteparin showed comparable aXa pharmacodynamics after IV and SC injection. By measuring the aIIa activities after IV administration of the LMMHs, T1/2, Amax, and AUC were comparable but tPC differed. After SC injection the aIIa activities of the LMMHs exhibited comparable T1/2 and Amax but different AUC and tPC. The plasma concentrations of the LMMHs showed comparable T1/2 but certoparin exhibited a higher Amax and AUC after IV and SC administration. The relative bioavailability of the aXa activity, aIIa activity, and the plasma concentrations ranged between 70 and 100%. The differences in the aIIa pharmacodynamic and pharmacokinetic profiles of certoparin and dalteparin may be caused by the differences in the in vitro activities and the different molecular mass. Clinical relevance of the different pharmacologic profiles is only expected of the aIIa activity-related biological effects of the LMMHs.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Comparison of the Pharmacodynamic and Pharmacokinetic Profiles of Two Low-Molecular-Mass Heparins in Rats

Piazolo

Harenberg²,

Malsch³

et al. 1997

Semin Thromb Hemost

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“…Very few patients qualify for nonsurgical treatment since conservative management is reported to have high failure rates. 7 Even though enoxaparin is reported to accumulate in the spleen preferentially, 12 , 13 the data on apixaban or its mechanism is currently unavailable. Multiple systemic diseases like polycythemia vera, chronic pancreatitis, pancreatic cancer, or splenic flexure colon tumor can affect and damage the architecture of the spleen making it fragile and vulnerable to minor trauma.…”

Section: Discussionmentioning

confidence: 99%

Atraumatic Splenic Rupture in a Patient on Apixaban and Dual Antiplatelet Therapy

Natarajan

Thangarasu

Ruck

et al. 2021

Journal of Investigative Medicine High Impact Case Reports

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Splenic rupture due to any cause is a life-threatening complication and commonly attributed to trauma. Atraumatic splenic rupture is very rarely reported, and the incidence is currently unknown. Anticoagulants and dual anti-platelet medication can increase the chances of a splenic rupture. Surgical removal of the spleen may be warranted to prevent a life-threatening bleeding. Early identification and intervention are required for most patients as only a few qualify for medical management.

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“…In this study, orally administered radiolabelled LHD was mostly distributed in the liver, spleen, and kidneys but not in the plasma or gastrointestinal tract. Therefore, the biodistribution of LHD might exhibit a similar pattern to that of LMWH (45,46).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic evaluation of an oral tablet form of low-molecular-weight heparin and deoxycholic acid conjugate as a novel oral anticoagulant

Park¹,

Jeon²,

Kim³

et al. 2011

Thromb Haemost

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This study was designed to develop a solid oral dosage form of deoxycholic acid (DOCA)-conjugated low-molecular-weight heparin (LMWH) and to evaluate its oral absorption, distribution, and metabolic stability for the prospect of providing an orally bioavailable LMWH. The LMWH derivative (LHD) was synthesised and then formulated with solubilisers and other pharmaceutical excipients to form a solid tablet. Its absorption and distribution after oral administration were evaluated in mice, rats, and monkeys. The in vitro metabolic stability of LHD was examined by liver microsome assays. More than 80% of LHD was released from the tablet within 60 minutes, guaranteeing rapid tablet disintegration after oral administration. Oral bioavailability of LHD in mice, rats and monkeys were 16.1 ± 3.0, 15.6 ± 6.1, and 15.8 ± 2.5%, respectively. After the oral administration of 131I-tyramine-LHD, most of the absorbed drug remained in the blood circulation and was eliminated mainly through the kidneys. LHD was hardly metabolised by the liver microsomes and showed a stable metabolic pattern similar to that of LMWH. In a rat thrombosis model, 10 mg/kg of orally administered LHD reduced thrombus formation by 60.8%, which was comparable to the anti-thrombotic effect of the subcutaneously injected LMWH (100 IU/kg). Solid tablets of LHD exhibited high oral absorption and statistically significant therapeutic effects in preventing venous thromboembolism. Accordingly, LHD tablets are expected to satisfy the unmet medical need for an oral heparin-based anticoagulant as an alternative to injectable heparin and oral warfarin.

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Pharmacokineties and tissue distribution of 99mTc-labelled enoxaparin in the rat: evaluation of dosimetry parameters

Cited by 9 publications

References 10 publications

Comparison of the Pharmacodynamic and Pharmacokinetic Profiles of Two Low-Molecular-Mass Heparins in Rats

Comparison of the Pharmacodynamic and Pharmacokinetic Profiles of Two Low-Molecular-Mass Heparins in Rats

Atraumatic Splenic Rupture in a Patient on Apixaban and Dual Antiplatelet Therapy

Pharmacokinetic evaluation of an oral tablet form of low-molecular-weight heparin and deoxycholic acid conjugate as a novel oral anticoagulant

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