• YAKHAK HOEJI
• /
• v.42 no.4
• /
• pp.431-436
• /
• 1998

The pharmacokinetics of CKD-602, a new camptothecin anticancer derivative, were studied in mice, rats and dogs following a single or multiple intravenous administration, and the following results were obtained. The blood levels of CKD-602 declined in biphasic fashions with peak plasma levels $(C_0)$ of $2.63{\mu}g/ml$ in mice, $2.27{\mu}g/ml$ in tumor bearing mice, $2.84{\mu}g/ml$ in rats at a dose of 20mg/kg, and of 0.02mcg/ml in dogs at a dose of 0.5mg/kg. The plasma half-lives $(t_{1/2}{\beta})$ were 9.55hr in mice, 9.94hr in tumor bearing mice, 9.98hr in rats and 12.75hr in dogs. AUC of CKD-602 was increased linearly with the dose at a range from 5 to 20mg/kg. Moreover, Cltot and Vdss were also not significantly changed with increasing the dose. On the other hand, after 5 daily intravenous bolus injection of CKD-602 (5mg/kg) in rats, $t_{1/2}{\beta}$, AUC and MRT of CKD-602 were 11.90hr, $3.19{\mu}g{\cdot}hr/ml$, and 11.61hr, respectively, which were slightly higher than after the single bolus injection.

• Journal of Pharmaceutical Investigation
• /
• v.39 no.5
• /
• pp.367-372
• /
• 2009

A rapid liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay method was developed for the determination of topotecan levels in rat serum. The assay utilized a single liquid-liquid extraction with a mixture of ethy l acetate and acetonitrile (6:1 v/v) and isocratic elution. The multiple reaction monitoring was based on the transition of m/z 422.0$\rightarrow$376.5 for topotecan and 315.1$\rightarrow$226.6 for clomipramine (internal standard). The developed assay was validated to demonstrate the specificity, recovery, lower limit of quantification (LLOQ), accuracy and precision. The assay was linear over a concentration range from 0.5-100 ng/mL, with LLOQ being 0.5 ng/mL using a small volume of rat serum (0.1 mL). The mean intra- and inter-day assay accuracy was 87.7-111.0% and 97.8-108.3, respectively, and the mean intra- and interday precision was between 1.6-4.3% and 3.8-10.3, respectively. The developed assay was applied to a pharmacokinetic study after a bolus i.v. injection of topotecan in rats.

• Biomedical Science Letters
• /
• v.3 no.2
• /
• pp.83-88
• /
• 1997

In septic patients, disseminated intravascula. coagulation (DIC) occurs frequently and is a pathologic condition associated with a variety of critical illness. DIC may complicate the already complex clinical situations and contribute to the high mortality. Nevertheless, its pathogenic mechanisms are not completely elucidated. Present study was prospectively designed to understand the pathogenetic mechanisms involved in the development of DIC. 15 rats were subjected to study and according to the aim, they were divided into three groups： group I, control (not treated-endotoxin, n=5)； group II (12 hours after endotoxin injection, n=5)； group III (24 hours after endotoxin injection, n=5). Experimental DIC was induced in rats by a bolus injection of endotoxin (1mg/kg, E. coli serotype 055:B5). Blood was collected by direct puncture of the heart. Platelet count, fibrinogen and plasminogen concentration, antithrombin III, D-dimer and complement components (C3 and C4) were measured in all subjects. In group II and III, there were apparent signs of DIC, including thrombocytopenia, decreased fibrinogen (but increase in group III), reduced C3 and antithrombin III, and elevated D-dimer. These data indicated that endotoxin might induce the activation of several pathways such as coagulation, fibrinolytic and complement cascade, causing DIC and subsequent multiple organ failures. Ultimately, the increased knowledge of the various pathogenetic mechanisms of coagulation activation and fibrinolysis in endotoxin-induced DIC may have prophylactic or therapeutic implications.

• The Korean Journal of Pain
• /
• v.20 no.2
• /
• pp.169-173
• /
• 2007

Background: Although the use of intravenous patient controlled analgesia (IVPCA) has been compared to the use of patient conrolled epidural analgesia (PCEA), there is no optimal administration route of alfentanil for the treatment of postoperative pain. This randomized double-blind study compared the efficacy of the use of IVPCA and PCEA for postoperative pain and the side effects after a total abdominal hysterectomy (TAH). Methods: Sixty patients undergoing a TAH were randomly assigned to receive either IVPCA (Group I) or PCEA (Group E) for the infusion of alfentanil for postoperative pain control. In both groups, a loading dose of $750{\mu}g$ alfentanil was administered. All patients received the same continuous infusion rate (0.3 mg/h), bolus dose (0.15 mg), and lockout time (15 min). The incidence of side effects, the VAS (visual analog scale) of pain, blood pressure, and heart rate were checked for 20 hours after the loading dose injection. Results: The VAS of pain was not significantly different between the two groups of patients. The onset of the analgesic effect was significantly more rapid in the Group I patients than in the Group E patients. There was no difference in side effects for either group. Conclusions: When considering multiple factors such as the onset of analgesia, technical difficulties or infection after the procedure, IVPCA using alfentanil is more useful than PCEA for postoperative pain control after a TAH.