ORAL ADMINISTRATION OF PENICILLIN IN CORN OIL AND LANOLIN

Oral administration of penicillin suspended in equal parts of corn oil and lanolin extends the maintenance of the penicillin level in the system (as determined by urine bio-assay). Measurable quantities were found 24 to 42 hours after ingestion. Recovery of the penicillin is about five times higher than under administration in saline solution. We wish to express our sincere appreciation to the various members of our staff who volunteered as subjects for these experiments.     

ORAL PENICILLIN

It is possible to attain serum concentrations of penicillin after oral administration comparable to those attained after intramuscular injection by the use of approximately five times as much penicillin. As the concentrations attained following the ingestion of penicillin by four different methods were all of the same order of magnitude, it would seem that the present problem in oral administration is analogous to that with intramuscular administration, i.e., to find the ideal vehicle whereby the duration of the serum concentration can be prolonged.     

ORAL PENICILLIN--A COMPARISON OF VARIOUS MODES OF ADMINISTRATION

A comparison of penicillin excretion when equivalent quantities of the drug are given orally or parenterally indicates that approximately 60 per cent. urinary excretion occurs after parenteral administration, whereas 14 per cent. urinary excretion occurs following oral ingestion. That destruction by gastric acidity is not primarily responsible for this difference is indicated by the fact that administration of penicillin directly into the duodenum does not greatly alter the amount of penicillin excretion. Evidence indicating that the majority of orally administered penicillin is destroyed by the body proper is discussed.     

ORAL PENICILLIN WITH BASIC ALUMINUM AMINOACETATE

This method appears to be suitable for the oral administration of penicillin. Basic aluminum aminoacetate seems admirably suited for this purpose. It is neutral and buffers gastric acidity to pH 4 to 4.5. While this work was in progress McDermott et al.(6) successfully employed magnesium trisilicate in this manner. Clinical work is now in progress using the combination in infections known to be susceptible to parenteral penicillin therapy.     

猪静脉注射青霉素G钾的药物动力学参数

本文对青霉素G钾在猪体内的药物动力学特征进行了分析,6头猪体重29.3±1.1kg(平均值±标准差),按每kg体重静脉注射单剂量青霉素G钾15000IU,给药后分别在0,5,10,15,30,45min及1,1.5,2,3h收集血样,采用微生物法测定血清青霉素G的浓度。以电子计算机程序处理血药浓度—时间数据,血药浓度随时间变化符合二室开放模型,所得主要动力学参数为:分布半衰期(t1/2α)0.14±0.03h;消除半衰期(t1/2β)0.70±0.21h;表观分布容积(Vd)0.696±0.141 l/kg;体清除率(Cls)11.67±1.02 ml/(kg·min);药时曲线下面积(AUC)21.57±1.93h·IU/ml,本文还根据单剂量给药参数推算给药方案,供兽医临床参考。     

猪肌注和鸡口服烟酸诺氟沙星后的药物动力学研究

湖北白猪８头单次肌内注射烟酸诺氟沙星１０ｍｇ／ｋｇ后，利用高效液相色谱法分析血浆中诺氟沙星的浓度，其检测限可达２５ｎｇ／ｍｌ血浆。房室模型分析表明，其吸收、分布和消除半衰期（Ｔ１２Ｋａ、Ｔ１２α、Ｔ１２β分别为（０．０４３４±０．０１１９）ｈ、（０．３０７８±０．１２２１）ｈ和（３．３４４６±０．１８８９）ｈ，最大血药浓度（Ｃｍａｘ）为（２．３６８０±０．４１１９）μｇ／ｍｌ，达峰时间（Ｔｍａｘ）为（０．２７±０．０４）ｈ，稳态血药浓度（Ｃｓ，τ＝１２ｈ）为（０．７０７±０．１２７）μｇ／ｍｌ。ＡＡ肉鸡８只口服烟酸诺氟沙星１０ｍｇ／ｋｇ后，药物在体内呈现单室模型过程，其吸收半衰期和消除半衰期（Ｔ１２Ｋａ、Ｔ１２Ｋｅ）分别为（０．８２３２±０．４０６２）ｈ和（３．４９７７±０．２８２３）ｈ，Ｃｍａｘ为（０．２２０９±０．０４０６）μｇ／ｍｌ，Ｔｍａｘ为（２．３１５９±０．６６３８）ｈ，平均稳态血浆药物浓度（Ｃｓ，τ＝１２ｈ）为（０．１３８０±０．０２３５）μｇ／ｍｌ。根据其药物动力学特征参数制订了猪肌注和鸡口服烟酸诺氟沙星的给药方案。     

鸡静注和口服盐酸沙拉沙星的药物动力学研究

伊利莎蛋鸡８只单次快速静脉注射盐酸沙拉星１０ｍｇ／ｋｇ后,利用高效液相色谱法测定血清中沙拉星的浓度。房室模型分析表明;血药浓度－时间数据适合无吸收因素二室模型,其消除半误期,表观分布容积,总体清除率和药时曲线下面积分别为（２．４７±０．８７Ｏｈ,（５．１０±２．２５）Ｌ／ｋｇ,（１．４２±０．２４）Ｌ／ｋｇ．ｈ和（７．２７±１．３７）μｇ／ｍｌ．ｈ。     

静注和口服盐酸沙拉沙星的药物动力学研究

伊利莎蛋鸡8只单次快速静脉注射盐酸沙拉星10 mg/kg (以沙拉沙星计)后,利用高效液相色谱法测定血清中沙拉星的浓度.房室模型分析表明:血药浓度时间数据适合无吸收因素二室模型,其消除半衰期(t1/2β)、表观分布容积(Vd)、总体清除率(CLB)和药时曲线下面积(AUC)分别为 (2.47±0.87O h、(5.10±2.25) L/kg、(1.42±0.24) L/kg.h和(7.27±1.37) μg/m l.h.伊利莎蛋鸡8只口服盐酸沙拉沙星溶液10 mg/kg (以沙拉沙星计)后,药物在体内呈现有吸收单室模型,其吸收半衰期(t1/2ka)、消除半衰期(t1/2ke)、血药达峰时间(Tmax )、药峰浓度(Cmax)和药时曲线下面积分别为(0.32±0.15) h、(3.68±0.89) h、(1.25±0.35) h、(0.86±0.28)μg/ml和(5.53±1.95)μg/ml.h.鸡内服盐酸沙拉沙星混悬剂(以淀粉混)10 mg/kg (以沙拉沙星计)后,药物吸收不规则,统计矩理论分析表明:药时曲线零阶矩(AUC)、药时曲线一阶矩(MRT, 平均驻留时间)和消除半衰期(t1/2ke)分别为(1.03±0.27)μg/ml.h、(6.22±0.76) h和(2.81±0.59)h.鸡内服盐酸沙拉沙星溶液剂后的生物利用度(F)为76.03%, 内服盐酸沙拉沙星淀粉混悬剂的生物利用度(F)仅为14.22%.     

INCREASING AND PROLONGING BLOOD PENICILLIN CONCENTRATIONS FOLLOWING INTRAMUSCULAR ADMINISTRATION

(1) Restriction of fluid intake to 1,500 cc and the salt intake to 3 gm a day doubles the penicillin blood level following interrupted intramuscular [See Figure in the PDF file] injections of penicillin. (2) The administration of benzoic acid to a patient on an unrestricted diet Ilay double the penicillin blood level during similar treatment. (3) The combination of these two procedures results in a four- to eight-fold increase in penicillin blood level with a prolonged effective blood concentration.     

猪链球菌病对肌肉注射多剂量青霉素G药物动力学的影响

本文报道猪链球菌病对肌肉注射多剂量青霉素G钾（15000IU/kg,每隔12h肌注1次,连续给药5次）在猪体内血清浓度和药物动力学影响的研究。通过皮下接种9-10亿个菌落形成单位的猪链球菌,人工诱发猪链球菌病。发病猪给药前的直肠体温比正常时至少升高1.5℃,第一次给药后8h内感染猪的直肠温度仍显著升高（P＜0.05或0.01）,并可观察到其他临床症状。给药后的不同时间间隔从前腔静脉采血,用微生物法测定血清青霉素G的浓度。病猪第一次给药和第五次给药后的血药浓度--时间数据用MCPKP计算机程序处理,均符合一级吸收二室开放模型。病猪第一次及第五次给药的主要药物动力学参数（平均值±标准差）分别是：t#-(1/2α)0.66±0.15及0.59±0.17h;t#-(1/2β)1.87±0.55及2.18±0.97h;t#-(1/2ka)0.35±0.05及0.20±0.09h（P＜0.05）;t#-(max)0.71±0.10及0.48±0.11h（P＜0.05）;C#-(max)7.48±0.97及9.04±0.62IU/ml（P＜0.01）;AUC16.84±1.64及16.42±1.65I U·h/ml,Tcp(ther)11.72±3.33及12.41±3.62h;笔者对引起病猪第一次及第五次给药的某些药物动力学参数有显著差异的原因进行了探讨。     

IN VITRO EVIDENCE OF REGENERATION OF ACTIVE PENICILLIN FROM PENICILLIN ESTERS

It has been found that methyl and ethyl esters of penicillin may be hydrolyzed in vitro to yield 26 and 16 per cent. respectively of the theoretical bacteriostatically active penicillin.