近年, 緑膿菌を中心とするグラム陰性桿菌によるOpportunistic infectionの増加に伴い, アミノ配糖体剤 (AGs) 使用の機会は増加している。特に, AGsは腎から尿中への移行が極めて良好であり, 基礎疾患を有する難治性の尿路感染症においては, 抗緑膿菌作用を有するAGsが第1選択となる場合も少なくない。本邦では, AGsの投与経路として臨床上筋注だけしか許可されていないが, 欧米では抗緑膿菌作用を有するAGsの静注も許可されている1)。出血傾向のある患者や, 重症例については, 明らかに静注のほうが望ましい投与法と考えられ, 本邦においてもここ数年来AGsの静注投与に関する基礎的, 臨床的検討が行われている2～4)。
今回, 我々は複雑性尿路感染症患者13例を対象として, Micronomicin (MCR) の点滴静注による治療を行い, その臨床効果並びに安全性について検討を加えたので報告する。

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第1報1)にてCefaclor (ケフラール®, 塩野義製薬, CCL) の使用経験を報告し, 投与期間に制限を設けない投与方法では, 単純感染症の26例で100% (平均7.3日間投与), そして複雑感染症の41例で80% (平均9.1日間投与) の総合有効率を得て, 副作用は消化器系症状が8.4%に認められたことを述べた。その後, 更に症例を重ねて検討したので報告すると共に, 1.CCL投与既往のある症例, 2.第3相2)及び第4相試験として本剤の効果と安全性を検討した報告3)と共に考察を加えたい。

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MT-141; Sodium (6R, 7S)-7-[(2S)-2-amino-2-carboxyethylthioacetamido]-7-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl) thio] methyl]-8-oxo-5-thia-1-azabicyclo-[4.2.0] oct-2-ene-2-carboxylate (Fig. 11))は, 明治製菓中央研究所において合成されたCephamycin系新抗生物質であり, 水に溶けやすい, 白色の結晶性粉末である。
本剤は各種細菌産生のβ-Lactamaseに対し安定であり, グラム陽性菌及びグラム陰性菌に対し, 広範な抗菌スペクトラムを有し, 又, Bacteroides fragilis, Clostridium difficille等の嫌気性菌に対しても優れた抗菌力を有すると報告されている2, 3)。
又, 7位側鎖にアミノ酸を含み, 且つメトキシ基を持つ構造に起因すると思われる抗菌機序上の特徴が認められ, 感染治療実験においてMICより推定される以上の効果 (ED₅₀) を示している4)。
毒性に関しては, LD₅₀はマウス, ラットともに5g/kg以上であり5), 亜急性6), 慢性毒性7)とも特異的な作用は認められないと報告されている。
本剤の一般薬理作用の一部については, すでに報告されており, 中枢, 呼吸, 循環器系に対しては特異的な作用がないことが判明している8)が, 今回, 体性神経系, 平滑筋, 消化管系その他について検討し, 若干の知見を得たので報告する。

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Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic3, 4) isolated from a culture broth of Streptomyces mycarofaciens1, 2). MOM is metabolized into 4 main metabolites of Mb₁, Mb₂, Mb₅, and Mb₁₂5).
The object of this study was to evaluate acute toxicity in male and female mice after single oral administration of Mb₁, a metabolite of MOM, at a dose level of 5,000 mg/kg as the maximum physically applicable dose.
Observations were kept for I week after administration. In conclusion, Mb₁ exhibited no acute toxicity in present study.
The LID₀ values were estimated as more than 5,000 mg/kg.

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Vol. 37 (1984) No. 5 p. 862-912
修正箇所：その他

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Acute toxicity studies on miocamycin (MOM), non-crystalline solid6), and its metabolite Mb₁7) were performed in mice in the previous studies.
In the present studies, we evaluated acute toxicity of Mb₁ in male and female rats after single oral administration at the maximum physically applicable dose of 5,000 mg/kg.
Observations were continued for 1 week after treatment. It is concluded that LID₀ values of Mb₁ were estimated more than 5,000 mg/kg.

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Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic isolated from a culture broth of Streptomyces mycarofaciens1), 2). It is reported that MOM has the most interesting antibacterial properties among macrolide antibiotics3, 4) and is metabolized into 4 main metabolites of Mb₁, Mb₂, Mb₆ and Mb₁₂5). It is also known that LD₀ values of Mb₁ were estimated more than 5,000 mg/kg without exhibiting any manifest toxic effects after single oral administration to male and female rats6).
The object of this study was to examine toxicological effects in male and female rats after repeated oral administration of Mb₁, a metabolite of MOM, for 5 weeks at daily dosages of 125, 250, 500 and 1,000 mg/kg which were selected in consideration of the maximum tolerable dosage level of 1,000 mg/kg/day for MOM, non-crystalline solid, in the rat subacute toxicity studies as previously reported7).

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Miocamycin (MOM) is a derivative of midecamycin1, 2) and is metabolized into 4 main metabolites5). At previous study, LD₀ values of Mb₁ were estimated more than 5,000 mg/kg in male and female mice7).
The object of this study was to evaluate acute toxicity in male and female mice after single oral administration of Mb₂, a metabolite of MOM, at a does level of 5,000 mg/kg as the maximum physically applicable dose. It is concluded that LD, values of Mb₂ were estimated more than 5,000 mg/kg.

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Miocamycin (MOM) is a derivative of midecamycin1), 2) and is metabolized into 4 main metabolites5). At previous study, LD₀ values of Mb₁, were estimated more than 5,000 mg/kg in male and female rats8).
The object of this study was to evaluate acute toxicity in male and female rats after single oral administration of Mb₂, a metabolite of MOM.
It is concluded that LD₀ values of Mb₂ were estimated more than 5,000 mg/kg.

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Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic and is metabolized into 4 main metabolites of Mb₁, Mb₂, Mb₆ and Mb₁₂.
At previous study, the acute and subacute toxicity of Mb₁ and acute toxicity of Mb₂ were performed that those metabolites did not exhibit any lethal toxicity even at the maximum physically applicable dose.
The object of this study was to examine subacute toxicity in male and female rats after repeated p. o. administration of Mb₂ for 5 weeks at a daily dosage of 125,250,500 and 1,000mg/kg.
It is, therefore, concluded that Mb₂, exerted no toxic effects in this subacute toxicity.

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Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites5).
In the present studies, we evaluated acute toxicity and estimated LD₅₀ values of Mb₆, one of the main metabolites of MOM, in male and female mice after single oral administration. Observations were continued for 1 week after treatment. The LD₅₀ values were calculated according to LITCHFIELDWILCOXON's method. It is concluded that LD₅₀ values of Mb₆ were 4, 150mg/kg (3,577.6-4, 814.0mg/kg) in male mice and 4,000mg/kg (3,389.8-4, 720.0mg/kg) in female mice, respectively.

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Miocamycin (MOM) is a derivative of midecamycin1, 2) and is metabolized into 4 main metabolites of Mb₁, Mb₂, Mb₆ and Mb₁₂5).
In the previous studies, we estimated LD₅₀ values of Mb₆ in male and female mice7) after single oral administration. The LD₅₀ values were 4, 150mg/kg in male mice and 4,000mg/kg in female mice, respectively.
In the present studies, we evaluated acute toxicity and estimated LD₅₀ values of Mb₆ in male and female rats after single oral administration.
Observations were continued for 1 week after treatment.
It is concluded that LD₀ values of Mb₆ in male and female rats, were estimated more than 5,000mg/kg as Mb₆ did not exhibit any manifest acute toxicity even at the maximum physically applicable dose of 5,000mg/kg.

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Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites of Mb₁, Mb₂, Mb₆ and Mb₁₂(5). It is also known that LD₅₀ values of Mb₆ were 4, 150mg/kg in male mice⁸ and 4,000mg/kg in female mice but LD₀ values in male and female rats were estimated more than 5,000mg/kg.6) The object of this study was to examine subacute toxicological effects in male and female rats after repeated oral administration of Mb₆ for 5 weeks at a daily dosage of 125, 250, 500 and 1,000mg/kg. It is concluded that no manifest toxicity was observed in this study with Mb₆ in male and female rats after oral administration at dosage levels of 125, 250, 500 and 1,000mg/kg for 5 weeks.

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We evaluated acute toxicity and estimated LD₅₀ values of Mb₁₂, one of the main metabolites of MOM, in male and female mice after single oral administration. Observations were continued for 1 week after treatment. The LD₅₀values were calculated according to LITCHFIELD-WILCOXON'S method.
It is concluded that LD₅₀ values of Mb₁₂ were 5,750mg/kg (4,914.5-6,727.5mg/kg) in male mice and 4,950mg/kg (4, 194.9-5,841.0mg/kg) in female mice, respectively.

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Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites of Mb₁, Mb₂, Mb₆ and Mb₁₂5). In the previous studies, LD₅₀ values of Mb₁₂7) were 5,750mg/kg in male mice and 4,950mg/kg in female mice, respectively.
The object of this study was to evaluate acute toxicity in male and female rats after single oral administration of Mb₁₂. Observations were continued for 1 week after treatment. It is concluded that LD₀ values of Mb₁₂were estimated more than 5,000mg/kg.

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Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic isolated from a culture broth of Streptomyces mycarofaciens1, 2). It is reported that MOM has the most interesting antibacterial properties among macrolide antibiotics3, 4) and is metabolized into 4 main metabolites of Mb₁, Mb₂, Mb₆, and Mb₁₂5). It is also known that LD₀ values of Mb₁₂ were estimated more than 5,000mg/kg without exhibiting any manifest toxic effects after single oral administration to male and female rats6).
The object of this study was to examine toxicological effects in male and female rats after repeated oral administration of Mb₁₂, a metabolite of MOM, for 5 weeks at a daily dosage of 125, 250, 500 and 1,000mg/kg which were selected in consideration of the maximum tolerable dosage level of 1,000mg/kg/day in MOM rat subacute toxicity studies as previously reported7).

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SUTHERLAND1) and WEISS et al.7) reported cases of newborn human deaths or GRAY syndrome after overdosage of chloramphenicol. In general, it has been reported that the acute toxicities of drugs are enhanced in immature animals compared with adult animals.
The objective of this study was to determine the LD₅₀ values in infant (5-day-old) and young adult (5-week-old) male and female mice after single subcutaneous and oral administration of MOM, noncrystalline solid and to estimate the toxicity ratio of those LD₅₀ values.
LD50 values of MOM, non-crystalline solid, were more than 5,000mg/kg and the lethal toxicity was the same in infant and adult mice. Toxicity ratios were not obtained.

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In the present acute toxicity studies on MOM, non-crystalline solid, with infant male and female rats (5-day-old) and young adult male and female rats (5-week-old), it is confirmed as follows:
1. LD₅₀ values were estimated more than 5,000mg/kg in both cases of subcutaneous and oral administrations.
2. MOM, non-crystalline solid, did not exhibit any toxic effects similarly as previously reported with infant male and female mice and young adult male and female mice.
3. There might be no definite age difference in toxicity between young and adult rats as LD₅₀ values were estimated more than 5,000mg/kg in independence upon the age.
4. There might be no definite species difference in toxicity between mice1) and rats.

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Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic isolated from a culture broth of Streptomyces mycarofaciens. The objective of this study was to determine the effect of MOM on reproductive performance in rats and rabbits. MOM, non-crystalline solid, was suspended in 0.1% CMC solution immediately before use.
In this study, reproductive performance was studied according to the following designs:
1. Fertility test (Segment I) in Wistar rats
2. Teratogenicity test (Segment II) in Wistar rats
3. Peri-and post-natal tests (Segment III) in Wistar rats
4. Behavioral test in rat newborns in Segments II and III
5. Teratogenicity test (Segment II) in New Zealand white rabbits
In conclusion, MOM, non-crystalline solid, might have no teratogenesis and little influence on dams and their fetuses and offsprings.

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