Comparison of pharmacodynamics between low dose ticagrelor and clopidogrel after loading and maintenance doses in healthy Korean subjects.

The novel antiplatelet agent ticagrelor has been demonstrated to exert a faster and more powerful inhibition of platelet aggregation in comparison to clopidogrel in coronary artery disease patients. However, a ticagrelor dose of 90 mg twice daily might not be suitable for patients of East Asian ethnicity, and has not been fully investigated. The aim of this study was to assess the effects of low loading doses (LD, 90 mg) and maintenance doses (MD, 90 mg daily) of ticagrelor in comparison to clopidogrel (600 mg LD, 75 mg daily MD) in healthy Korean volunteers. Twelve subjects were randomized into two groups, receiving either clopidogrel (600 mg LD, followed by 75 mg MD daily for 5 days) or ticagrelor (90 mg LD, followed by 90 mg MD daily for 5 days). Following a 2-week washout period, the treatments were switched between the groups. Three platelet function assessment methods which included light transmission aggregometry (LTA), the VerifyNow assay and multiple electrode platelet aggregometry (MEA) were then used to serially measure platelet function at various time points (baseline, 0.5, 2, 6, 24, 26, 120 and 122 h). The mean IPA to 10 µM ADP in the ticagrelor group was significantly higher than that for the clopidogrel group at the 0.5, 2, 6, 26 and 122 h time points (p ≤ 0.001). However, there was no significant difference between the two groups at the 24- and 120-hour time points (p > 0.05). The assay results produced by the other two platelet function tests (VerifyNow and MEA) were similar to those obtained by LTA. The low loading and maintenance doses of ticagrelor (90 mg LD, 90 mg daily MD) cause a more rapid and potent inhibition of platelet function when compared to clopidogrel (600 mg LD and 75 mg MD). Additionally, at the lowest value of platelet inhibition strength, oral once-daily administration of ticagrelor was no less efficacious than clopidogrel at the 24- and 120-hour time points. Due to a large diurnal variation occurring with a single daily dose, a lower dose twice-daily could be a better option for patients of East Asian ethnicity.

Lower loading dose of prasugrel compared with conventional loading doses of clopidogrel and prasugrel in korean patients undergoing elective coronary angiography: a randomized controlled study evaluating pharmacodynamic efficacy.

BACKGROUND AND OBJECTIVES: Although prasugrel allows for rapid and potent platelet inhibition, the efficacy and safety of lower doses of prasugrel for patients of East Asian ethnicity has not yet been investigated. We compared the effect of a lower loading dose (LD) of prasugrel with conventional LDs of clopidogrel and prasugrel in Korean patients. SUBJECTS AND METHODS: Forty-three Korean patients undergoing coronary angiography were enrolled in the study. Participants were randomly administered LDs of clopidogrel 600 mg, prasugrel 30 mg or prasugrel 60 mg prior to coronary angiography. Platelet reactivity was assessed at baseline and at the time of peak platelet inhibition using light transmission aggregometry (LTA), the VerifyNow assay, and multiple electrode aggregometry. RESULTS: Although baseline platelet reactivity between the groups showed no significant differences, at the time of peak platelet inhibition, the prasugrel 30 mg (18.9±10.0%) and 60 mg groups (13.8±10.8%) showed significantly more potent platelet inhibition than the clopidogrel 600 mg group (52.9±15.8%; p<0.001) by LTA. However, there were no significant differences between the prasugrel 30 mg and 60 mg groups (p=0.549). CONCLUSION: The loading effect of prasugrel 30 mg was more potent than clopidogrel 600 mg and was not significantly different from prasugrel 60 mg.

Reduced valproic acid serum concentrations due to drug interactions with carbapenem antibiotics: overview of 6 cases.

BACKGROUND: The plasma concentrations of valproic acid (VPA) are known to decrease during the concomitant administration of carbapenem antibiotics, such as meropenem, imipenem, and ertapenem. This study summarizes 6 cases of drug-drug interactions between VPA and carbapenem antibiotics. METHODS: To investigate the onset and severity of the reductions in the concentration of VPA in patients with or without the coadministration of carbapenem antibiotics, the authors performed a retrospective evaluation of therapeutic drug monitoring (TDM) reports that described a decrease in the serum concentrations of VPA during the concomitant use of carbapenem antibiotics from January 2008 to December 2010 in the Seoul National University Hospital. The evaluated TDM reports included 6 cases. The decrement ratio of the VPA serum concentration was calculated from the TDM reports, and the change in the half-life of the VPA was also estimated. RESULTS: Six cases presented with changes in the VPA serum concentration before and after the administration of carbapenem antibiotics. (Three cases were treated with meropenem, 2 were treated with ertapenem, and 1 was treated with imipenem.) The VPA concentrations reduced by (mean ± SD) 88.7 ± 5.3% (3 cases of meropenem), 74.0 ± 9.8% (2 cases of ertapenem), and 73.3% (1 case of imipenem), respectively, and the half-life of VPA reduced by 80.1 ± 9.0%, 64.4 ± 24.2%, and 50.6%, respectively. CONCLUSION: The interaction between VPA and carbapenem antibiotics caused decreases in the VPA serum concentrations; the extent of this decrease was greater in the meropenem-treated patients than in the imipenem-treated or ertapenem-treated cases. Because the therapeutic effect of VPA depends on its serum concentration, it should be recognized that there may be a loss of seizure control in patients using VPA with carbapenem antibiotics.