• Biomolecules & Therapeutics
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• 제4권4호
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• pp.411-414
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• 1996

Single subcutaneous administration to S.D rats of both sexes was performed to investigate the acute toxicity of Syndella gel, a new topical drug containing deproteinised dialysate of calf's blood and micronomicin sulfate. $LD_{50}$ values for S. D rats were 23,047 mg/kg for male and 23,725 mg/kg for female. The death occurred within 24 hours after administration at doses over 19,200 mg/kg. The main cause of death seemed to be respiratory disturbance by acute shock. Major general symptoms induced by injection subcutaneously with Syndella gel were underactivity, decreased respiratory rate, salivation, tremor and loss of consciousness. No significant body weight changes and gross findings of internal organs in treatment groups in comparison with those of control groups was observed at any dose levels in Syndella gel.

• Journal of Veterinary Science
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• 제22권5호
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• pp.47.1-47.10
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• 2021

Background: Due to multiple similarities in the structure and physiology of human and pig skin, the pig model is extremely useful for biological drug testing after subcutaneous administration. Knowledge of the differences between subcutaneous injection sites could have a significant impact on the absorption phase and pharmacokinetic profiles of biological drugs. Objectives: This study aimed to analyze the impact of administration site on pharmacokinetics and selected biochemical and hematological parameters after a single subcutaneous administration of ustekinumab in pigs. Drug concentrations in blood plasma were analyzed by enzyme-linked immunosorbent assay. Pharmacokinetic analyses were performed based on raw data using Phoenix WinNonlin 8.1 software and ThothPro v 4.1. Methods: The study included 12 healthy, female, large white piglets. Each group received a single dose of ustekinumab given as a 1 mg/kg subcutaneous injection into the internal part of the inguinal fold or the external part of the inguinal fold. Results: The differences in absorption rate between the internal and external parts of the inguinal fold were not significant. However, the time of maximal concentration, clearance, area under the curve calculated between zero and mean residence time and mean residence time between groups were substantially different (p > 0.05). The relative bioavailability after administration of ustekinumab into the external part of the inguinal fold was 40.36% lower than after administration of ustekinumab into the internal part of the inguinal fold. Conclusions: Healthy breeding pigs are a relevant model to study the pharmacokinetic profile of subcutaneously administered ustekinumab.

• Biomolecules & Therapeutics
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• 제1권2호
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• pp.280-283
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• 1993

Single subcutaneous injection to SD rats of both sexes was performed to investigate the acute toxicity of new skin allergy-remedy ointment, Banaron. Banaron is composed of lidocaine hydrochloride, chloro-pheniramine maleate, prednisolone acetate, chlorohexidine hydrochloride, methyl salicylate, 1-menthol and d-camphor. The results were as fellows. $LD_{50}$, /TEX> values of Banaron were 8373.6 mg/kg for male and 8260.1 mg/kg for females. Death occurred within 24 hours after administration at doses up to 6600 mg/kg. The main cause of deaths seemed to be respiratory disturbance. General symptoms decreased of activity and respiratory rate, salivation, tremor and loss of consciousness which were commonly observed by some survived animals and all dead animals. No significant gross findings of internal organs and body weight changes in treatment groups in comparison with these of control group were observed at the maximum dose levels in Banaron.

• Biomolecules & Therapeutics
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• 제5권4호
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• pp.380-383
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• 1997

CJ-50001 is a recombinant granulocyte-colony stimulating factor (rG-CSF) developed by Cheil Jedang R&D Center. The effects of CJ-50001 on the increase of peripheral neutrophil count following intravenous and subcutaneous single administration at a dose of 20$\mu$g/kg in normal ICR mice and SD rats, respectively, were compared with those of Grasin, a control drug. Both CJ-50001 and Grasin significantly increased the peripheral neutrophil number in four treatment groups and the maximum number of neutrophil was achieved at 12 to 18 h in rats and mice, respectively. The dose dependency test was studied for CJ-50001 only in normal mice by intravenous or subcutaneous administration. When administered i.v or s.c at the various doses in normal mice, CJ-50001 significantly increased the neutrophil number over the dose of 160 ng/kg, compared with the vehicle control group. From these results, it was concluded that CJ-50001 showed efficacy similar to Grasin in the peripheral neutrophil count increase.

• Biomolecules & Therapeutics
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• 제6권4호
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• pp.400-405
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• 1998

The pharmacokinetics of CJ-50001 (recombinant human granulocyte-colony stimulating factor, developed by R&D center of Cheil Jedang Corp.) were investigated in rats and dogs. The serum concentrations of CJ-50001 were measured by a sandwich enzyme immunoassay. After single intravenous (iv) administration of Cf-50001 to rats at a dose of 5 $\mu$g/kg, the mean terminal half-life and area under the concentration-time curve (AUC) were 0.96 h and 124.497g . h/ml, respectively. After single subcutaneous (sc) administration at the same dose, maximum serum concentration was observed at about 2 hours after administration, and the mean terminal half-life, AUC and the bioavailability were 1.11 h,63.58$\mu$g . h/ml and 51.07%, respectively. In repeated dosing studies, CJ-50001 was administered iv and sc to rats at a daily dose of 5$\mu$g/kg for 7 days. The pharmacokinetic parameters, such as mean AUC and terminal half-life, were no significantly different from those of single administration. Following single iv and sc administration of CJ-50001 to dogs at a dose of 5 $\mu$g/kg, mean AUCs were much higher than those of rats, due to the decreased clearence (CL). After sc administration to dogs, maximum serum concentration was observed at 2~4 hours after administration and the bioavailability was 54.60%.

• Clinical and Experimental Pediatrics
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• 제56권3호
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• pp.116-124
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• 2013

Purpose: Tumor necrosis factor (TNF)-${\alpha}$ is thought to contribute to pulmonary hypertension. We aimed to investigate the effect of infliximab (TNF-${\alpha}$ antagonist) treatment on pathologic findings and gene expression in a monocrotaline-induced pulmonary hypertension rat model. Methods: Six-week-old male Sprague-Dawley rats were allocated to 3 groups: control (C), single subcutaneous injection of normal saline (0.1 mL/kg); monocrotaline (M), single subcutaneous injection of monocrotaline (60 mg/kg); and monocrotaline + infliximab (M+I), single subcutaneous injection of monocrotaline plus single subcutaneous injection of infliximab (5 mg/kg). The rats were sacrificed after 1, 5, 7, 14, or 28 days. We examined changes in pathology and gene expression levels of TNF-${\alpha}$, endothelin-1 (ET-1), endothelin receptor A (ERA), endothelial nitric oxide synthase (eNOS), matrix metalloproteinase (MMP) 2, and tissue inhibitor of matrix metalloproteinase (TIMP). Results: The increase in medial wall thickness of the pulmonary arteriole in the M+I group was significantly lower than that in the M group on day 7 after infliximab treatment (P<0.05). The number of intraacinar muscular arteries in the M+I group was lower than that in the M group on days 14 and 28 (P<0.05). Expression levels of TNF-${\alpha}$, ET-1, ERA, and MMP2 were significantly lower in the M+I group than in the M group on day 5, whereas eNOS and TIMP expressions were late in the M group (day 28). Conclusion: Infliximab administration induced early changes in pathological findings and expression levels of TNF-${\alpha}$, and MMP2 in a monocrotaline-induced pulmonary hypertension rat model.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.251-251
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• 1996

-Acute oral and subcutaneous toxicity of Aloewhite(30% aloesine) were carried out in ICR mice. In this study, we daily examined number of deaths, clinical signs, body weights, and pathological examinations for 14 days after single oral and subcutaneous administration of Aloewhite with different dose levels. Aloewhite did not show any remarkable toxic effect in mice. These results suggest that oral and subcutaneous LD$\sub$50/ values in mice were over 6.8g/kg and 10g/kg, respectively.

• Journal of Veterinary Science
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• 제21권2호
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• pp.32.1-32.13
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• 2020

Levofloxacin pharmacokinetic profiles were evaluated in 6 healthy female rabbits after intravenous (I/V), intramuscular (I/M), or subcutaneous (S/C) administration routes at a single dose of 5 mg/kg in a 3 × 3 cross-over study. Plasma levofloxacin concentrations were detected using a validated Ultra Performance Liquid Chromatography method with a fluorescence detector. Levofloxacin was quantifiable up to 10 h post-drug administration. Mean AUC_0-last values of 9.03 ± 2.66, 9.07 ± 1.80, and 9.28 ± 1.56 mg/h^*L were obtained via I/V, I/M, and S/C, respectively. Plasma clearance was 0.6 mL/g*h after I/V administration. Peak plasma concentrations using the I/M and S/C routes were 3.33 ± 0.39 and 2.91 ± 0.56 ㎍/mL. Bioavailability values, after extravascular administration were complete, - 105% ± 27% (I/M) and 118% ± 40% (S/C). Average extraction ratio of levofloxacin after I/V administration was 7%. Additionally, levofloxacin administration effects on tear production and osmolarity were evaluated. Tear osmolarity decreased within 48 h post-drug administration. All 3 levofloxacin administration routes produced similar pharmacokinetic profiles. The studied dose is unlikely to be effective in rabbits; however, it was calculated that a daily dose of 29 mg/kg appears effective for I/V administration for pathogens with MIC < 0.5 ㎍/mL.

• Biomolecules & Therapeutics
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• 제2권3호
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• pp.247-255
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• 1994

As a series of safety studies of DA-3030, a new rhO-CSF, its local irritancy was examined in the rabbits after the following treatment; application into the conjunctival sac of the eye(single), subcutaneous injection(single), intramuscular injection(single), and intravenous injection(8-day repeated). In addition, paravenous irritation of DA-3030 was investigated in mice. The results obtained were as follows. 1. In the result of ocular irritation test, 0.03% solution of DA-3030 could be considered as a non-irritating material. 2. The local irritation of DA-3030 by an injection of 0.5mι of its solution subcutaneously or intramuscularly was negligible and not so much different from that of saline. 3. In the vascular irritancy test, macro- and microscopic observations revealed that the irritating activity of DA-3030 in blood vessels was not different from that of saline when they were injected once a day into vein retroauricularis of rabbits for 8 days.4. The paravenous administration of DA-3030 did not induce any abnormal changes at injection sites except mild swelling in 1 mouse at 3 hours after injection which was thought to be due to slow absorption. The above-mentioned results suggest that DA-3030 has no irritating activity when injected through intravenous or subcutaneous route for clinical practice as 0.03% solution.

• Toxicological Research
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• 제14권3호
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• pp.393-400
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• 1998

As a series of safety studies on DA-3585, a recombinant human erythropoietin, its local irritancy was examined in rabbits after the following treatments; application into the conjunctival sac of the eye(single), subcutaneous injection (single and -day repeated)and intravenous injection (7-day repeated.)In addition, perivascular irritation of DA-3585 was investigated in mice. In the result of ocular irritation test, 10,000IU/ml solution of DA-3585 could be considered as a non-irritating material. The local irritation of DA-3585 by a single and 7-day repeated subcutaneous injection was negligible and not so much different from that of saline. In the vascular irritancy test, macro-and microscopic observations revealed that local irritation of DA-3585 was comparable to that of saline when injected into retroauricular vein of rabbits for 7 consecutive days. Furthermore the perivascular administration of DA-3585 upto the concentration of 10,000 IU/ml did not induce any morphological abnormalities at injection sites. The results obtained from the present study suggest that the local irritancy of DA-3585 is not different from that of saline when injected through intravenous or subcutaneous route for clinical practice.