VOL. 28 S-2 CHEMOTHERAPY

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CHEMOTHERAPY JULY 1980 Enterobacter cloacae, Escherichia coli Klebsiella pneumeinae Fig. 1 Chemical structural formula of cefadroxil

VOL. 28 S-2 CHEMOTHERAPY

CHEMOTHERAPY JULY 19 80 Table 1 Effect of cefadroxil on ether anesthesia and pentobarbital sleep in mice Table 2 Effect of cefadroxil on pentetrazol convulsion in mice * Rates are expressed as No. of inhibited / No. of tested.

Table 3 Effect of cefadroxil on pain response in mice Rates are expressed as No. of depressed f No. of tested. Fig. 2 Effect of cefadroxil and 7% sodium bicarbonate on the blood pressure and respiration of the rabbit

CHEMOTHERAPY 66 Fig. 3 Effect of cefadroxil on the blood pressure (Sensitivity to acetylcholine) Fig. 4 Effect of cefadroxil on the blood pressure (Sensitivity to adrenaline) JULY1980 and respiration and respiration of the rabbit of the rabbit Fig. 5 Effect of cefadroxil of the blood pressure of the rabbit (Sensitivity to acetylcholine and adrenaline)

VOL,28 CHEMOTHERAPY S-2 Table 化 は み ら れ ず,心 に,ほ 4 Effect 拍 数 に 対 し て もTable4に of cefadroxil しめす よ う と ん ど 影 響 を 与 え な か っ た な お,7%炭 酸水素 ナ ト リ ウ ム 液 も心 電 図 お よ び 心 拍 数 に 対 し,ほ 響 を 与 え な か っ た CDXは 量 は100mg/kgを 溶 解 性 の 点 か ら,そ 最 高 限 度(炭 用 量:50 56mg/kg)と 3.摘 と ん ど影 の適用 酸 水 素 ナ ト リウムの 適 した 出 モ ル モ ッ ト心 房 に 対 す る 作 用 CDX10-6 5x10-3g/mlTyrode液 モ ッ ト心 房 の 自 動 運 動(振 適 用時 の摘 出 モル 幅 お よ び 拍 動 数)は,Fig.6 に しめ す よ うに,5x10-4g/ml以 下 の 濃 度適 用 例 で は ほ とん ど 影 響 を 与 え な か っ た 10-3g/ml以 上 の濃 度 適 用 例 で は 濃 度 に ほ ぼ 比 例 し て 振 幅 は 減 少 し た が.拍 動数に は ほ と ん ど変 化 は な か っ た こ の よ うな 作 用 はTyrode 液 で 洗 滌 す る と速 や か に 回 復 した な お,振 はFig.7に 67 on heart rate of rabbit 0.1 1.000μg適 用 例 で は 色 素 透 過 開 始 時 間 お よ び30分 後 の 色 素 透 過 度 はLocke液 と 同 程 度 で あ り,CDXは III.平 1,摘 滑 筋 に及 ぼ す 影 響 出 腸 管 に 対 す る作 用 a.単 独作用 i.摘 出 ウサ ギ 腸 管 CDX10-7 5 10-3g/ml ギ 腸 管 の 自 動 運 動(振 め す よ うに,10-3g/ml以 Tyrode液 Effect atrium 管 に 対す る作 用 a.摘 出 ウサ ギ耳 殻 血 管 灌 流量 CDX10-6 2x10-2g/ml Locke液 ギ 耳 殻 血 管 灌 流 量(1分 前処置 適 用 前58.9滴/分 で あ り,ほ れ な か っ た な お,CDXは 濃 度 は2 10-2g/mlを 濃度適 と ん ど変 化 は み ら 溶 解 性 の 点 か ら,そ の適用 最 高 限 度 と した サ ギ 皮膚 血 管透 過 性 CDX0.1 1,000μg 対 照 と し てLocke液,さ 1μgの し め す よ うに. に 対 し,10-6 2 10-2g/mlの 用 例 で は58.9 60.0滴/分 b.ウ 適 用時 の摘 出 ウサ 間)は,Fig.8に Locke液 適 用 時 の 色 素 透 過 度 を, ら に,Hist.10μgお そ れ と比 較 した Fig.9に よ びAch し め す よ う に,CDX Fig. 7 Effect of cefadroxil on the isolated atrium (Pretreated with atropine) 上の濃度適用例 of cefadroxil on the isolated of the guinea pig に よ っ て 影 響 され な か っ た 4.血 し 下 の 濃 度 適 用例 では ほ と ん ど 変 化 は み ら れ な か った 2 10-3g/ml以 Fig. 6 適 用時 の摘 出 ウサ 幅 お よ び 筋 緊 張)は,Fig.10に 幅抑制作用 し め す よ うに,atropine10-4g/mlの 皮 膚 血 管透 過 性 に 対 し影 響 を与 え なか った of the guinea pig

CHEMOT 68 Fig. 8 Effect ear of cefadroxil HERAPY on Ow rabbit JULY1980 Fig. 9 vessels Fig. Fig. 11 10 Effect Effect of cefadroxil of cefadroxil on on the the isolated isolated Effect of cefadroxil of the rabbit intestine intestine of of the skin on vessels rabbit guinea pig permeability

VOL.28 S-2 CHEMOTHERAPY Fig. 12 Effect of cefadroxil on the isolated intestine of the guinea pig (Combination with histamine) Fig. 13 Effect of cefadroxil on the isolated intestine of the guinea pig (Combination with histamine, acetylcholine or barium chloride) Histamine Acetylcholine Barium chloride (5 ~10-9g/ml)(2 ~10-8g/ml) (5 ~10-10g/ml)(10-9g/ml) (5 ~10-6g/ml)

CHEMOTHERAPY JULY 1980 Fig. 14 Effect of cefadroxil on the isolated trachea of the guinea pig Fig. 15 Effect of cefadroxil on the isolated uterus of the rat

VOL.28 S-2 CHEMOTHERAPY * Score 3 according et al. 9) to the method of KAUZMANOFF Fig. 16 Effect of cefadroxil on the isolated pregnant uterus of the rat Table 5 Effect of cefadroxil on paralytic action in mice Table 6 Effect of cefadroxil on cornea reflex in the rabbit,

CHEMOTHERAPY JULY 1980 Table 7 Urinary excretion of electrolytes and urinary findings in the rat applied per as cefadroxil once a day for 7 days Urinary findings: ph6.0 `7.0 protein 25-60 mg/100ml ketone body 0-5 mg/100m1 glucose negative urobilinogen 0.5-1.0 11/100011 Occult blood negative *Maximum levels are indicated in the maximum decrease or increase during the drug administration as well as that applied time in parenthesis. Table 8 Pharmacological effects of cefadroxil Table 9 Pharmacological effects of cefadroxil

CHEMOTHERAPY

CHEMOTHERAPY JULY 1980 Streptococcus pyrogenes 0.19 `0.39 Đg/ml, Klebsiella pneumoniae 1) BUCK, R. E. & K. E. PRICE: Cefadroxil, a new broad-spectrum cephalosporin. Antimicr. Agents & Chemoth. 11: 324-330, 1977 2) PFEFFER, M.; A. JACKSON, J. XIMENES & J. P. DE MENEZES: Comparative human oral clinical pharmacology of cefadroxil, cephalexin, and cephradine. Antimicr. Agents & Chemoth. 11: 331-338, 1977 3) Report of Bristol: Cefadroxil (BL-S578). 7) BURGISON, R. M.: Animal techniques for evaluating anticonvulsant, in pharmacologic techniques in drug evaluation. ed. by J. H. Nordine & P. H. Siegler, p. 348, Year Book Medical Publishers, Inc., Chicago, 1964 8) EDDY, N. B. & D. LitimsAcs Synthetic analgesics. II. Dithienylbutenyl and dithienylbutylamines. J. Pharmacol. Exp. Ther. 10: 385 ` 393, 1953 9) TisLow, R. F.: Evaluation of sedative-hypnotics in the course of psychopharmacological testing. in selected pharmacological testing methods. vol. 3, ed. by A. Burger, p. 421, Marcel Denker, Inc., N. Y., 1968 PHARMACOLOGICAL STUDIES ON CEFADROXIL REPORT 1. GENERAL PHARMACOLOGY HARUE ARATANI, SHIZUKO KONO, HIDEKI TATEISHI and YASUMITSU YAMANAKA* Department of Pharmacology, Hiroshima University School of Medicine and *Department of Pharmacology, Medical College of Oita Cefadroxil (CDX), a new cephalosporin antibiotic for oral administration, was investigated on its general pharmacology. 1. CDX was given orally in mice at a dose of 4,000 mg/kg, and no effect of the drug was observed on ether anesthesia, pentobarbital sleep, pentetrazol convulsions, analgesic action and muscle-relaxing action. 2. CDX was investigated in situ and in vitro on the effects upon autonomic nervous system. No effect of the drug was observed on blood pressure, respiration and ECG at a dose of 100 mg/kg. Inhibitory action in vitro was generally observed on isolated organs at a concentration of more than 500 pg/ml. 3. CDX was given in rats for 7 days at a dose of 100 mg/kg, and no influence was noted on urinary excretion and its electrolytes.

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