• Toxicological Research
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• 제20권4호
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• pp.375-380
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• 2004

The toxicity of CKD-602 was investigated at doses of 0, 3, 9, and 27 mg/kg in rats, by administering the same total dose over 24-hr continuous infusion or bolus injection. CKD-602 treatment caused gastrointestinal symptoms such as diarrhea, soft stool, and soiled perineal region. It also decreased body weight at doses of 9 and 27 mg/kg in a dose-dependant manner. At 3 mg/ kg, clinical signs and body weight decrease were more severe in the infusion group than in the bolus group. In the bolus group, mortalities were 0/8, 0/8, 1/8, and 3/8 at 0, 3, 9, and 27 mg/kg, respectively, whereas those were 0/8, 1/8, 8/8, and 8/8 in the infusion group. $LD_{50}$ values were 36.25 mg/kg for bolus and 3.50 mg/kg for infusion, respectively. This finding indicates that the toxic potency of CKD-602 by continuous infusion is about 10 times higher than by bolus injection. Our findings suggest that the toxic effects of CKD-602 are dependant upon the duration of intravenous administration.

• 약학회지
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• 제42권4호
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• pp.431-436
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• 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.

• Toxicological Research
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• 제20권4호
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• pp.381-389
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• 2004

The toxicity of CKD-602 was investigated at doses of 3, 9, and 27 mg/kg in rats, when the same total dose of CKD-602 was administered over 24 hr-continuous infusion or bolus injection. At 3 and 9 mg/kg, the 24-hr infusion group showed a more decreased WBC count on day 3, compared with the bolus group. Administration of CKD-602 caused more toxic effects such as the significant decreases of RBC counts, hematocrit, hemoglobin, and platelet count on day 7 post-administarion in the 24-hr infusion group than in the bolus group. Administration of CKD-602 also caused histopathological changes such as extramedullary hemopoiesis of liver and spleen, hyperplasia of femoral bone marrow, and caecal dilation. These toxic effects were more severe in the 24-hr infusion group than in the bolus injection group, indicating that the toxicity of CKD-602 may be dependant upon the duration of administration.

• The Korean Journal of Pain
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• 제10권1호
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• pp.42-47
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• 1997

Background : This study was designed to evaluate the continuous effects of single intravenous injection of antiemetics on nausea and vomiting during continuous morphine injection for postoperative pain control. Methods : Prior to the study, we divided patients into two major groups according to the type of surgery performed intra-abdominal(Open: O) and non intra-abdominal(Close: C). When patients regained orientation after routine general anesthesia, enflurane-$O_2-N_2O$, we injected bolus dose of morphine and started continuous injection of morphine for postoperative pain control(Group I; Control). After bolus injection and just before continuous injection, we injected single dose of droperidol(Group II) or ondansetron(Group III). Mean arterial blood pressure, heart rate, pain score and symptom-therapy score were checked at 10 minutes, 4, 8, 16, 24, 36 hours after continuous morphine injection. Results : The pain score of group III was lower than group II(10 min.) and group I(24, 36 hours) in the open group. Symptom-therapy score of group III(10 min., 4, 24 hours) and group II(10 min.) were lower than group I in the open group. In the close group, symptom-therapy score of group III(8 hours) was lower than group I. Conclusions : Single intravenous injection of antiemetics have a tendency of lowering symptom-therapy score for 36 hours in spite of their relatively short elimination half-life.

• 대한수의학회지
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• 제45권2호
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• pp.263-271
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• 2005

To compare the sedative effects using intermittent intravenous bolus injection with tiletamine-zolazepam (n = 5, TZ group), xylazine-ketamine (n = 5, XK group) and propofol (n = 5, PI group), we investigated the changes of hemodynamic (heart rate, arterial pressure), $SpO_2$, rectal temperature, respiratory rate and pain score during 60 minute sedation and 40 minute recovery period in beagle dogs. The value of rectal temperature was significantly higher in PI groups (p<0.05) during recovery period. The value of heart rate was significantly lower in XK group (p<0.05) during sedation. The changes of respiratory rate were similar tendency in all groups. The change of $SpO_2$ was stable during sedation and value was significantly higher in PI group (p<0.05) during recovery period. The value of systolic arterial pressure (SAP) was significantly lower in XK group (p<0.05) than PI group during sedation and recovery period. Low analgesic effect occurred in PI group. We concluded that intravenous anesthesia by intermittent bolus injection with propofol is useful in stabilizing rectal temperature, $SpO_2$ and hemodynamic during sedation and provide fast recovery, but have low analgesic effect.

• 한국임상수의학회:학술대회논문집
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• 한국임상수의학회 2006년도 춘계학술대회
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• pp.136-136
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• 2006

• Journal of Gastric Cancer
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• 제16권3호
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• pp.177-181
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• 2016

Purpose: The International Organization for Standardization-5fluorouracil (FU) 10 trial found that bolus 5-FU and l-leucovorin was not inferior to S-1 in the treatment of gastric cancer (GC). Continuous 5-FU and the rapid injection of 5-FU have different anti-cancer effects. Thus, bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. Materials and Methods: We retrospectively analyzed the medical records of all patients with S-1 or capecitabine-resistant, unresectable, or recurrent GC treated with bolus 5-FU and l-leucovorin between January 2010 and December 2015 at Hokkaido University Hospital. The bolus 5-FU and l-leucovorin regimen consisted of intravenous l-leucovorin ($250mg/m^2/2h$) and bolus 5-FU ($600mg/m^2$) administered once weekly followed by a 2-week rest period; each cycle was repeated every 8 weeks. Results: A total of 14 patients were identified. The disease control rate was 35.7%. The median progression-free survival was 1.6 months (95% confidence interval [CI], 1.3~2.0 months), and the median overall survival was 6.3 months (95% CI, 4.7~7.9 months). No patient died from treatment-related causes. The most common severe adverse event associated with bolus 5-FU and l-leucovorin was neutropenia, which occurred in 21.4% of patients. Conclusions: Bolus 5-FU and l-leucovorin treatment might be useful for oral FU-resistant GC. We are planning a multi-center prospective phase II trial to evaluate the efficacy and safety of bolus 5-FU and l-leucovorin treatment for pre-treated unresectable or recurrent GC to confirm the results of this limited, retrospective study.

• Archives of Pharmacal Research
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• 제21권4호
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• pp.411-417
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• 1998

In order to investigate the effect of the pretreatment with various doses of diltiazem (DTZ) on the pharmacokinetics of indocyanine green (ICG) at steady state, especially the hepatic blood clearance due to the change of hepatic blood flow, the following experiments were carried out with ICG, a hepatic function test marker, not metabolized in liver and only excreted in bile. The intravenous bolus injection ($3,780\mu\textrm{g}$/kg) and the constant-rate infusion ($10,100\mu\textrm{g}$/kg/hr) of ICG into the left femoral vein were made in order to check the steady-state plasma concentration ($C_{ss} of $10\mu\textrm{g}$/ml) of ICG at 20, 25 and 30 min. Following a 90-min washout period, the intravenous bolus injection (108, 430, 860 and $1,720\mu\textrm{g}$/kg) and the constant-rate infusion (108, 433, 866 and $1,730\mu\textrm{g}$/kg/hr) of DTZ into the right femoral vein were made and the achievement of the steady-state plasma levels ($C_{ss} of 50, 200, 400 and 800 ng/ml) of DTZ were conformed at 60, 70 and 80 min. During the steady state of DTZ, the intravenous bolus injection ($3,780\mu\textrm{g}$/kg) and the constant-rate infusion ($10,200\mu\textrm{g}$/kg/hr) of ICG into the left femoral vein were made and also the steady-state plasma concentration of ICG was checked at 20, 25 and 30 min. The plasma concentrations of DTZ and ICG were determined using a high performance liquid chromatographic technique. At the steady state, the hepatic blood clearance of ICG was obtained from the plasma concentration and blood-to-plasma concentration ratio ($R_B$) of ICG. The pretreatment with various doses of DTZ did not influence the plasma concentrations, $R_B$ and plasma free fraction ($f_p$) of ICG. So the hepatic blood clearance of ICG was independent of concentration of DTZ. The hepatic blood clearance of ICG could be affected by both hepatic bood flow and hepatic intrinsic clearance. But there was no change of the hepatic blood clearance of ICG between the control and the DTZ-pretreated rats in this study. So it may be suggested that DTZ does not influence hepatic blood flow.

• 한국임상수의학회:학술대회논문집
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• 한국임상수의학회 2006년도 춘계학술대회
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• pp.133-133
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• 2006

• Journal of Veterinary Science
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• 제25권3호
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• pp.36.1-36.15
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• 2024

Importance: The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is an attractive treatment option. On the other hand, it can result in severe complications, including pulmonary thromboembolism (PTE). Objective: The present study assessed the occurrence of PTE after the intravenous infusion of canine AdMSCs (cAdMSCs) into experimental animals. Methods: Five-week-old male BALB/c hairless mice were categorized into groups labeled A to G. In the control group (A), fluorescently stained 2×10⁶ cAdMSCs were diluted in 200 µL of suspension and injected into the tail vein as a single bolus. The remaining groups included the following: group B with 5×10⁶ cells, group C with 3×10⁶ cells, group D with 1×10⁶ cells, group E with 1×10⁶ cells injected twice with a one-day interval, group F with 2×10⁶ cells in 100 µL of suspension, and group G with 2×10⁶ cells in 300 µL of suspension. Results: Group D achieved a 100% survival rate, while none of the subjects in groups B and C survived (p = 0.002). Blood tests revealed a tendency for the D-dimer levels to increase as the cell dose increased (p = 0.006). The platelet count was higher in the low cell concentration groups and lower in the high cell concentration groups (p = 0.028). A histological examination revealed PTE in most deceased subjects (96.30%). Conclusions and Relevance: PTE was verified, and various variables were identified as potential contributing factors, including the cell dose, injection frequency, and suspension volume.