J T Brandt

..Thienopyridines are prodrugs, metabolized in vivo to active metabolites that inhibit the platelet P2Y12 adenosine diphosphate (ADP) receptor...

..Switching directly from clopidogrel MD to either prasugrel LD or MD was well tolerated and resulted in significantly greater levels of platelet inhibition than a clopidogrel 75 mg MD...

..The determination of the clinical utility of such POC devices will require their use in clinical outcome studies...

..The overall data suggest that a prasugrel dose adjustment is not likely warranted in an individual taking prasugrel with a proton pump inhibitor such as lansoprazole...

..To investigate the potential effect of atorvastatin 80 mg/day on the pharmacokinetics and pharmacodynamics of the thienopyridines prasugrel and clopidogrel...

..The pharmacodynamic response to clopidogrel is more variable than the response to prasugrel, but the reasons for variation in response to clopidogrel are not well characterized...

..We conclude that CYP3A4 and CYP3A5 inhibition by ketoconazole affects formation of clopidogrel's but not prasugrel's active metabolite. The decreased formation of clopidogrel's active metabolite is associated with reduced IPA...

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..The pharmacokinetic (PK) and pharmacodynamic (PD) responses to prasugrel were compared in three studies of healthy subjects vs. those with moderate or end-stage renal impairment...

..In conclusion, greater exposure to prasugrel's active metabolite results in faster onset, higher levels, and less variability of platelet inhibition compared with high-dose clopidogrel in healthy subjects...

..Drotrecogin alpha (activated) (DAA) is a recombinant human activated protein C (APC), which is an antithrombotic protein. Objectives: To evaluate the development of anti-APC antibodies in severe sepsis patients in DAA clinical studies...

..Hydrolysis of urine samples appears necessary for optimal measurement of urine desmosine...

..Regardless of the criterion, prasugrel 60 mg achieved greater IPA and fewer poor responders than the clopidogrel 300-mg LD...

..After a thienopyridine LD, the initial rate of platelet inhibition was predictive of pharmacodynamic responder status...

..86, p < 0.0001). VASP and LTA demonstrated concordance across the response range of P2Y(12) receptor blockade following thienopyridine LDs...

..Objective thresholds for pharmacodynamic poor responders to clopidogrel should consider the concentration of the agonist used and may help assess the consistency of pharmacodynamic response to novel ADP receptor antagonists...

..Within the limitations of the study, prasugrel was found to be well tolerated when dosed as LD followed by MD in the presence of ASA and provided greater platelet inhibition than ASA alone...

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..Gender, race, body weight, and age were identified as statistically significant covariates impacting platelet inhibition...

..Prasugrel LDs and MDs provide rapid and sustained inhibition of ADP-mediated platelet aggregation...

..As a result, the use of affinity purified primate antibodies to determine the sensitivity of an immunogenicity assay will likely result in the true sensitivity of the assay being underestimated...

..Together, these findings indicate that a one-step assay format can greatly reduce the effect of coating concentration variation on assay performance...

..Efficient use of this platform requires process improvements to fully maximize the positive impact of multiplex assays in clinical drug development...

..Analysis of plasminogen and tPA gene alterations in patients with thrombophilia is also not warranted at this time. Determination of plasminogen concentration should be performed in patients suspected of having ligneous conjunctivitis...

..This study indicated that prasugrel 10 mg daily for 10 days was well tolerated and at steady-state provided sustained high levels of inhibition of platelet aggregation...

..In conclusion, prasugrel 30 and 75 mg were well tolerated and achieved a consistently high level of platelet inhibition with a fast onset of action...

..0007). CONCLUSION: In this population, prasugrel (40-60 mg LD and 10-15 mg MD) achieves greater IPA and a lower proportion of pharmacodynamic non-responders compared with the approved clopidogrel dosing...

..A fondaparinux standard curve should be used for reporting fondaparinux levels using an anti-factor Xa assay...

..3 to 30.9%). The reference materials used in the standard curves for immunoturbidometric vWF:Ag assays appear to have accurately assigned vWF values for the majority of commercial suppliers...

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