D S Small

..We aimed to characterize the pharmacokinetics and pharmacodynamics of drotrecogin alfa (activated) (recombinant human activated protein C) in patients with severe sepsis...

..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...

..This study evaluated the influence of ranitidine coadministration on the pharmacokinetics and pharmacodynamics of the respective active metabolite of prasugrel and clopidogrel...

..Prasugrel is a novel antiplatelet agent approved for the treatment of ACS patients undergoing percutaneous coronary intervention, and will be used in this population...

..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...

..We compared prasugrel pharmacokinetics, pharmacodynamics, and tolerability in healthy Chinese, Japanese, Korean and Caucasian subjects...

..Although the approved loading dose is 60 mg, earlier studies of prasugrel suggested that active-metabolite exposure and pharmacodynamic response may be higher in Asian subjects than in white subjects...

..These results characterize prasugrel's PK across a range of studies and highlight body weight as the most influential covariate on prasugrel AM exposure, with implications for prasugrel maintenance dosing in clinical practice...

..Although prasugrel did not alter warfarin pharmacokinetics, prasugrel and warfarin should not be used together, because of an increased bleeding risk associated with their concomitant use...

..As hepatic enzymes play a key role in formation of prasugrel's active metabolite, hepatic impairment could affect the safety and/or efficacy of prasugrel in such patients...

..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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..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...

..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...

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

..This integrated analysis supports the findings of earlier individual studies comparing these methodologies that assess platelet function...

..1%) was 30% (90% confidence interval [CI] 1.16-1.45) higher than exposure in patients > or =60 kg. Mean Pras-AM exposures for patients > or =75 years (10.5%) were 19% (90% CI: 1.11-1.28) higher compared with patients <75 years...

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

..The greater PD response with prasugrel compared with clopidogrel was accounted for by greater conversion of dose to active metabolite...

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

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

..To compare single- and multiple-dose duloxetine pharmacokinetics between healthy Japanese and Caucasians...

..These results are consistent with patients receiving prasugrel not requiring dose adjustments when treated with drugs primarily metabolized by CYP2B6...

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

..Hemostatic benefits of platelet transfusions in thienopyridine-treated acute coronary syndrome (ACS) patients may be compromised by residual metabolite in circulation...

..A large, phase 3, randomized, placebo-controlled study is ongoing to confirm these results and formally assess the safety and efficacy of drotrecogin alfa (activated) in children...

..1% CsA-treated patient. These results indicate that long-term use of topical CsA ophthalmic emulsions at doses that are clinically efficacious for treating dry eye will not cause any system-wide effects...