T.S. Kim

The Pharmacokinetics and Safety of a Fixed-Dose Combination of Acetylsalicylic Acid and Clopidogrel Compared With the Concurrent Administration of Acetylsalicylic Acid and Clopidogrel in Healthy Subjects: A Randomized, Open-Label, 2-Sequence, 2-Period, Single-Dose Crossover Study

BACKGROUNDnDual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is used for the treatment of acute coronary syndrome. A combined formulation of ASA and clopidogrel has been developed to provide dosing convenience and improve adherence.nnnOBJECTIVEnThis study was designed to compare the pharmacokinetic properties and safety profile of a fixed-dose combination formulation of ASA and clopidogrel with concurrent administration of each agent in healthy male Korean volunteers.nnnMETHODSnThis single-dose, randomized, open-label, 2-period crossover study was conducted in 64 healthy Korean volunteers. Equal numbers of eligible participants were randomly assigned to receive either the fixed-dose combination of ASA 100 mg and clopidogrel 75 mg or the free combination of each agent followed by a 7-day washout period and then administration of the alternate formulation. Serial blood samples were collected immediately before and after dosing for 24 hours. The safety profile was evaluated by using adverse events (AEs), which were assessed by physical examination, vital signs, ECGs, clinical laboratory tests, and interviews. The 2 formulations were considered to be bioequivalent if the 90% CIs for the log-transformed C(max) and AUC(0-last) values were within the predetermined range of 0.8 to 1.25.nnnRESULTSnSixty-four volunteers (mean [SD] age, 27.51 [8.15] years; weight, 68.55 [7.86] kg; height, 173.80 [5.94] cm) were enrolled, and 63 completed the study. For ASA, the 90% CIs for the geometric mean ratios of C(max) and AUC(0-last) were 0.9483 to 1.1717 and 0.9946 to 1.1020, respectively. For salicylic acid, the 90% CIs were 0.9614 to 1.0396 for C(max) and 0.9778 to 1.0163 for AUC(0-last). For clopidogrel, the 90% CIs were 0.9809 to 1.2562 for C(max) and 0.9674 to 1.2073 for AUC(0-last). Six of the 20 AEs reported were drug related: decreased hemoglobin levels (n = 2), fever (n = 1), and headache (n = 1) with the test formulation and increased alanine aminotransferase levels (n = 1) and dyspepsia (n = 1) with the reference formulation. All of the drug-related AEs were transient and mild in severity.nnnCONCLUSIONSnThe fixed-dose combination of ASA and clopidogrel 100 mg/75 mg did not meet the regulatory criteria for bioequivalence as defined by the Korea Food and Drug Administration. Both formulations were well tolerated in these healthy male Korean subjects. ClinicalTrials.gov Identifier: NCT01448330.

Effect of food on the pharmacokinetic properties of the oral sarpogrelate hydrochloride controlled-release tablet in healthy male Korean subjects.

BACKGROUNDnA new controlled-release formulation of sarpogrelate, a 5-hydroxytryptamine receptor subtype 2 antagonist that blocks serotonin-induced platelet aggregation, has been developed for once-daily administration.nnnOBJECTIVEnThis study evaluated the effect of food on the pharmacokinetic properties of controlled-release sarpogrelate (sarpogrelate CR) in healthy volunteers.nnnMETHODSnA randomized, open-label, two-period, two-treatment crossover study was performed in healthy male Korean subjects. Following an overnight fast, a single dose of sarpogrelate CR 300 mg was administered either in the fasted condition or immediately after a high-fat breakfast. Pharmacokinetic parameters were calculated using a noncompartmental analysis. Tolerability was determined using clinical laboratory testing and physical examination, including vital sign measurements, electrocardiography, and interviews with the volunteers regarding adverse events (AEs).nnnRESULTSnA total of 24 healthy subjects were enrolled, 23 of whom completed the study (mean [range] age, 26 years [21-45]; weight, 68.1 kg [56.0-79.9]; body mass index, 22.1 kg/m(2) [18.8-25.0]). Sarpogrelate C(max) and AUC(last) were decreased In the fed condition compared with those in the fasted condition, with geometric mean ratios (90% CI) of 0.4868 (0.4041-0.5864) and 0.7394 (0.6809-0.8028), respectively. T(max) was delayed from 0.75 to 4.0 hours after a high-fat meal, but the fed condition exhibited a similar elimination profile to that of the fasted condition. The most commonly reported AE was headache (n = 2), and other AEs were reported in 1 subject each. All of the AEs were considered mild in intensity, and the participants recovered without treatment.nnnCONCLUSIONSnCompared with the administration of sarpogrelate CR 300 mg in the fasted condition, administration with food was associated with a decreased rate and extent of absorption, as assessed by C(max) and AUC(last), respectively. The drug was well-tolerated by the healthy subjects in this study.

Effect of comedication on lamotrigine clearance in Korean epilepsy patients.

BACKGROUNDnLamotrigine (LTG) is a widely used antiepileptic-drug (AED) for the treatment of epilepsy. We investigated the effect of AED comedication on LTG clearance in Korean patients with epilepsy.nnnMETHODSnThe authors reviewed the medical charts for all patients≥18years who have received LTG as monotherapy or adjunctive therapy. Data collected included LTG levels, dosage, treatment duration, concomitant AEDs and specific side effects. LTG clearance was estimated according to comedication.nnnRESULTSnA total of 580 blood samples from 548 patients were analyzed. LTG clearance in the enzyme-inducing AED (EIAED) coadministration group was the highest (0.050l/kg/h), followed by the LTG monotherapy group (0.028l/kg/h), the coadministration group of both valproate (VPA) and EIAED (0.024l/kg/h) and the VPA coadministration group (0.018l/kg/h). When LTG was administered with both VPA and EIAED, the multiple EIAED group had higher LTG clearance than the single EIAED group.nnnCONCLUSIONSnConcomitant administration of valproate reduced LTG clearance by approximately 35%, while EIAEDs increased LTG clearance by 80%. These relationships indicate the importance of considering the effects of comedication on LTG clearance when determining LTG dosage.

Multiple tracheal metastases of lung cancer: CT and integrated PET/CT findings.

Multiple tracheal metastases of lung cancer: CT and integrated PET/CT findings E.Y. Kim , T.S. Kim *, J.Y. Choi , J. Han , H. Kim Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

Histologically benign but clinically malignant neoplasms in the thorax: CT-pathological overview.

The purpose of this article is to review the computed tomography (CT) and histopathological features of uncommon primary neoplasms of the thorax that can manifest clinically malignant features (multiplicity of pulmonary nodules, an invasive nature, and metastases or recurrence after surgery) with little evidence of histological malignancy.