56 CHEMOTHERAPY JAN Fig. 1 Effect of Mezlocillin on respiration, blood pressure and ECG in the rabbit

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1 VOL.27 S-1 CHEMOTHERAPY 55

2 56 CHEMOTHERAPY JAN Fig. 1 Effect of Mezlocillin on respiration, blood pressure and ECG in the rabbit

3 VOL.27 CHEMOT S-1 Fig. 2 Effect of Mezlocillin on blood pressure (Sensitivity Fig. 3 1 Effect よ びAd感 処 受 性 に ま っ た く影 響 を 与 ウサ ギ心 電 図に 対 す る作 用 Mezlocillinの50 400mg/kg適 心 電 図(第II誘 QRS間 った 3. rate of the rabbit 摘 出 モ ル モ ッ ト心 房 に 対 す る 作 用 Mezlocillinの g/ml 導)は は,Fig.4に 用 時 の無 麻 酔 ウサ ギ 各 棘 波 お よ び 波 形,PQ間 隔 に ほ と ん ど 変 化 は み ら れ ず,心 も,Table1に on heart of the rabbit Tyrode液 の 摘 出 モ ル モ ッ ト心 房 の 自動 運 動(振 え なか った 2. of the rabbit to acetylcholine) of Mezlocillin 昇 し た が,Mezlocillinの50mg/kg前 置 に よ り,Achお and respiration Effect of Mezlocillin on blood pressure and respiration (Sensitivity to adrenaline) Table 42mmHg上 57 HERAPY し め す よ うに,ほ 隔, 拍 数 に 対 して と ん ど影 響 を 与 え な か し め す よ う に,ほ 適用時 幅 お よ び 拍 動 数) とん ど変 化 は み られ な か っ た 4. a. 血 管 に対 す る作 用 摘 出 ウサ ギ耳 殻 血 管 灌 流 量 Mezlocillinの g/ml の,摘 出 ウ サ ギ 耳 殻 血 管 灌 流 量(1分 Locke液 間)は,Fig.5に 適用時

4 Fig. 4 Effect of Mezlocillin on the isolated atrium of the guinea pig Fig. 5 Effect of Mezlocillin on the rabbit ear vessels Fig. 6 Effect of Mezlocillin on permeability of the rabbit skin vessels

5 VOL.27 CHEMOT S-1 しめ す よ うに,適 /ml適 用 前61滴/分 用 例 で は61 65滴/分 い が,5 10-2g/ml適 に 対 し, g で あ り,ほ で あ り,6 10分 透 過 性 を,対 Fig.7に 後 に 回復 した b. Locke液 適用時の色素 ら に,Hist 用 例 で は,Locke液 で あ る が,1,000μg適 摘 出 モ ル モ ッ ト腸 管 しめ す う に,ほ と同一 程 度 2. 用 例 では 僅 か に 充 進す る傾 向を し Fig. 8 Fig. 9 Effect Effect of Mezlocillin of Mezlocillin of Mezlocillin 適用時 とん ど 変 化 は み られ な か っ た Mezlocillinの g/ml on the on the on the isolated isolated isolated しめ す よ 摘 出 モ ル モ ッ ト気 管 筋 に 及 ぼ す 影 響 用 時 の,摘 Effect Tyrode液 の 摘 出 モ ル モ ッ ト腸 管 の 筋 緊 張 は,Fig.8に め した Fig. 7 幅 お よ び 筋 緊 張)は, と ん ど変 化 は み ら れ な か っ Mezlocillinの /ml 10μg そ れ と比 較 し た Fig.6に よ う に μg適 し め す よ う に,ほ 適用時 た 照 と し てLocke液,さ お よ びAch1μgの Tyrode液 の 摘 出 ウ サ ギ 腸 管 の 自 動 運 動(振 でpeak ウサ ギ皮 膚 血 管透 過 性 Mezlocillinの0.1 1,000μg 摘 出腸 管 に対 す る作 用 摘 出 ウサ ギ腸 管 Mezlocillinの /ml と 管拡 張 作 用 のあ る こ と を み と め た そ の 際 の 経 時 的 変 化 は2分 平 滑筋 に及 ぼ す 影 響 1. a. 用 例 で は81滴/分 適 用 量 に ほ ぼ 比 例 し て 滴 数 が 増 加 し,血 b. II とん ど変 化 は な 用 例 で は70滴/分,10-lg/ml適 用 例 で は75滴/分,2 10-1g/ml適 59 HERAPY 出 モ ル モ ッ ト気 管 筋 緊 張 は,Fig.9に intestine intestine trachea Ringer-Locke液 of the of the of the rabbit guinea guinea pig pig 適 しめ

6 Fig.10 Effect of Mezlocillin on the isolated non pregnant uterus of the rat Fig.11 Effect of Mezlocillin on the isolated pregnant uterus of the rat Table 2 Effect of Mezlocillin on paralytic action in mice * Score 3 according to the method of KAUZMANOFF

7 Table 3 Effect of Mezlocillin on cornea reflex in the rabbit Table 4 Urinary excretion of electrolytes and urinary findings in the rat applied Mezlocillin subcutaneously once a day for 7 days Urinary findings: ph 6.1 `7.2 glucose 0 protein 25 `50 mg/100 ml urobilinogen 0.1 u/100 ml ketone body 0 `5 mg/100 mloccult blood 0 * Maximum levels are indicated the maximum decrease or increase during the drug administration well as that applied time in parenthesis., as

8 Table 5 General pharmacological properties of Mezlocillin and Carbenicillin 1) BODEY G. P. & T. PAN: Mezlocillin; In vitro studies of a new broad spectrum penicillin. Antimicrob. Agents Chemother. 11 : 74-79, ) KRASEMANN C.: In vitro activity of Mezlocillin and Azlocillin against gramnegative rods and grampositive cocci: 16th Interscience Conference on Antimicr. Agents & Chemoth. 346, ) WERNER H. & C. KRASEMANN : Susceptibility of Bacteroidaceae to Mezlocillin, Azlocillin and carbenicillin: 16 th Interscience Conference on Antimicr. Agents & Chemoth. 347, ) LODE H.; U. NIESTRATH, P. KOEPPE & H LANGMAACK: Clinical pharmacology of two new semi-synthetic penicillins: Mezlocillin and Azlocillin: 16 th Interscience Conference on Antimicr. Agents & Chemoth. 348, 1976

9 CHEMOTHERAPY 63 PHARMACOLOGICAL STUDIES ON MEZLOCILLIN, FIRST REPORT: GENERAL PHARMACOLOGY YASUMITSU YAMANAKA, SHIZUKO KONO, HIDEKI TATEISHI and HARUE ARATANI Department of Pharmacology, Hiroshima University, School of Medicine, Hiroshima, Japan The pharmacological actions of Mezlocillin, a new type of semisynthetic penicillin effective against severe infections by gram-negative bacilli, were investigated. Pharmacological actions and minimal effective doses (MED) were as follows: dilation of isolated rabbit ear vessels (5 ~10-2 g/ml), slight stimulation of permeability of rabbit abdominal skin vessels (1,000 Đg), inhibition of isolated guinea pig trachea (10-3 g/ml) and inhibition of isolated rat non-pregnant and pregnant uteri (10-3 and 2 ~10-3 g/ml). No effect was observed on rabbit blood pressure and respiration (100 mg/kg), on rabbit ECG (400 mg/kg), on isolated guinea pig atrium (5 ~10-3 g/ml), or isolated rabbit and guinea pig intestine (2 ~10-3 and 5 ~ 10-3 g/ml). Muscular paralysis and local anesthetic action were not observed in doses of 10 g/kg and 2 ~10-1 g/ml, respectively. MED of Mezlocillin were much larger than minimal inhibitory concentrations and maximal blood levels in clinical uses, and were similar to those of Carbenicillin. The increase in body weight, volume of urine, urinary excretion of sodium and potassium, and urinary findings in the rat applied Mezlocillin in doses from 25 to 100 mg/kg subcutaneously once a day for 7 days were similar to normal values and those of the control group.

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