Pharmacokinetics and Tolerability Evaluation of Fudosteine after Oral Administration in Healthy Korean Volunteers

BACKGROUND: Fudosteine, (-)-(R)-2-amino-3-(3-hydroxypropylthio)propionic acid, is a cysteine derivative that was approved in Japan, as a new mucoactive agent. The aim of this study was to evaluate the tolerability and pharmacokinetics (PK) of fudosteine in healthy Korean subjects. METHODS: A randomized, open-label, parallel, escalating single-dose study was conducted in 16 healthy Korean male subjects. The subjects were allocated to single-dose groups of 400 or 800 mg. Serial blood samples for PK analysis were collected immediately prior and after dosing up to 24 hours, and plasma concentrations were determined by high performance liquid chromatography (HPLC). Safety profiles were evaluated by monitoring adverse events and clinical evaluations throughout the study. RESULTS: Median time to peak concentration (Tmax) of both dosing group were around 0.5 hours and half-life (t1/2) were around 3 hours. Mean peak concentration (Cmax) of 400 mg and 800 mg dosing group were 10.8 and 21.5 microg/mL and the mean area under the plasma concentration versus time curve from the dosing time to infinity (AUCinf) were 26.8 and 55.0 microg.h/mL, respectively. Mean dose-normalized Cmax were 0.0271 and 0.0269 microg/mL/mg (P=0.923), respectively and dose-normalized AUCinf were 0.0669 and 0.0688 microg.hr/mL/mg (P=0.093), respectively. Fudosteine was well tolerated without any serious adverse events or clinical laboratory abnormalities. CONCLUSION: This study showed that fudosteine has a linear PK property and is well tolerated within 800 mg in healthy Korean volunteers.

Hepatitis B Reactivation During Adjuvant Anthracycline-Based Chemotherapy in Patients with Breast Cancer: A Single Institution's Experience

BACKGROUND: The objectives of this study were to determine the incidence, outcome and risk factors for HBV reactivation in HBsAg positive breast cancer patients while on anthracycline -based adjuvant chemotherapy. METHDOS: We retrospectively reviewed the records of 2,431 patients with early breast cancer who received adjuvant chemotherapy from March 2001 to December 2005. Among these patients, 111 HBsAg positive women were enrolled in this study. RESULTS: Thirty-seven patients (33.3%) developed acute hepatitis, of which 23 (20.7%) were related to HBV reactivation. Univariate analysis showed that an age > or =47 years (p=0.034) and abnormal sonographic findings such as a fatty liver or cirrhotic changes (p=0.034) were associated with HBV reactivation. However, an HBeAg positive status and the use of corticosteroids were not. Multivariate analysis found that no clinical factors could predict HBV reactivation during chemotherapy. All 23 patients who developed HBV reactivation received lamivudine as a therapeutic measure at the time of HBV reactivation. Despite the use of lamivudine, disruption in the chemotherapy protocol occurred in 18 patients (78.3%) and 14 of these patients had premature termination of their chemotherapy. CONCLUSIONS: HBV reactivation occurred in a significant proportion of HBsAg positive patients during adjuvant anthracycline-based chemotherapy. Once hepatitis developed, most patients could not finish the chemotherapy as planned despite lamivudine treatment. Until the risk factors for reactivation are clearly identified, HbsAg-positive patients should begin prophylactic antiviral treatment before initiating chemotherapy.

Gemcitabine Single or Combination Chemotherapy in Post Anthracycline and Taxane Salvage Treatment of Metastatic Breast Cancer: Retrospective Analysis of 124 Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy of gemcitabine- based chemotherapy, particularly in patients with anthracycline- and taxane-pretreated 2(nd)-line or greater metastatic breast cancer, and to compare gemcitabine monotherapy (G) with two gemcitabine-based doublets, gemcitabine/ vinorelbine (GV) and gemcitabine/capecitabine (GX). MATERIALS AND METHODS: Of 124 consecutive patients who progressed after anthracycline- and taxane-containing chemotherapy, 58 received G alone, 38 received GV, and 28 received GX; their outcomes were analyzed retrospectively. RESULTS: The median number of prior metastatic chemotherapy regimens was 2 (range 0~4). Visceral metastases were observed in 65 patients (51.4%). The overall response rate was 19.3% (21 partial responses). After a median follow-up period of 21.4 months, the overall survival was 7.6 months (95% CI: 5.5~9.6 months) and the median time to progression was 3.1 months (95% CI: 2.0~4.2 months). Compared with monotherapy (G), combination therapy with vinorelbine or capecitabine (GV/ GX) was associated with a significantly higher response rate (8.2% vs. 28.3%, p=0.008) and a significantly longer median time to progression (2.8 vs. 3.5 months; p=0.028), but overall survival did not differ between the groups (7.4 vs. 8.2 months, respectively; p=0.54). Most of the adverse treatment-related events were mild to moderate in intensity. The most common adverse event was hematologic toxicity. Multivariate analysis showed that poor performance status and a short disease-free interval were independent prognostic factors for impaired overall survival. CONCLUSIONS: The combination of gemcitabine with vinorelbine or capecitabine was an active and well-tolerated treatment option for taxane- and anthracycline-pretreated 2(nd)-line or greater metastatic breast cancer patients, and gemcitabine-based doublets were more beneficial than gemcitabine monotherapy in alleviating symptoms for these patients.

A Case Report of Electrical Burn by Ground Plate of Electrosurgical Unit / 대한마취과학회지

A electrical safety in the operating room is one of important responsibility for the anesthesiologists and surgeons. When the patient is included in an electric circuit with poor ground during operation under the general anesthesia electrical accident might be occurred, such as sustained muscular contration with asphixia, impairment of CNS function, ventricular fibrillation, and more commonly, burn and other physiological injuries. Authors report an electrical burn on the right calf area (3X5 cm) and both heels by ground plate of electrosurgical unit which is probably poor contacts with the patient and review about its prevention and safety of electric practice.