Pharmacokinetics of intramuscular carbenicillin in the newborn

Summary A 500 mg intramuscular dose of carbenicillin produced peak levels averaging 147µg/ml after three hours in the first day full-term newborn infants, and 172µg/ml after one to two hours in infants five days of age. The fall of blood levels thereafter was delayed and serum half-life averaged 4.2 and 2.2 hours in both groups, almost four times and twice as long, respectively, as that reported in adults. Absorption from the injected site was also delayed in young newborns, as was shown by the delayed serum peak and small estimated absorption rate constant. This must be taken into consideration if the intramuscular route is chosen in young newborn infants. On the basis of serum half-life, an administration interval of 12 hours was recommended for newborns younger than four days, and eight hours for those five days of age or more.

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Pharmakokinetik von intramuskulär verabreichtem Carbenicillin beim Neugeborenen

Zusammenfassung Die intramuskuläre Verabreichung von 500 mg Carbenicillin ergab eine maximale Serumkonzentration von im Mittel 147µg/ml nach drei Stunden bei reifen Neugeborenen am ersten Lebenstag, von 172µg/ml nach ein bis zwei Stunden bei Neugeborenen im Lebensalter von fünf Tagen. Der Abfall der Serumkonzentration war verzögert, die Serumhalbwertzeit betrug durchschnittlich 4,2 bzw. 2,2 Stunden in beiden Gruppen, sie war ungefähr vier- bis zweimal so lang wie der beim Erwachsenen angenommene Wert von etwa einer Stunde. Die Absorption aus der Injektionsstelle war auch beim jungen Neugeborenen verzögert, wie durch die verzögerte maximale Serumkonzentration und niedrige Absorptionsrate gezeigt wurde. Dies muß dann in Betracht gezogen werden, wenn der intramuskuläre Weg bei jungen Neugeborenen gewählt wird. Aufgrund der verlängerten Halbwertzeiten wird ein Dosierungsintervall von 12 Stunden bei Neugeborenen bis zu vier Tagen empfohlen, und ein Intervall von acht Stunden bei denen, die fünf Tage alt oder älter sind.

     

Factor-Xa Inactivation by Antithrombin III

S ummary . The inactivation of the procoagulant activity of bovine factor Xa by antiproteinase present in antithrombin III preparation follows the pseudo-first-order kinetics with respect to factor Xa. The rate of inactivation is devoid of the dimension of factor Xa concentration when antiproteinase in excess is held constant. In the presence of physiological concentrations of factor V, phospholipids and ionic calcium, the affinity of factor Xa for antithrombin III drastically decreases, and the half-life of the enzyme is very significantly prolonged. This biological stabilization of factor Xa requires the presence of all three substances: factor V, phospholipid and calcium. However, it is quantitatively dictated only by factor V concentrations. Calcium ions and phospholipid required for factor Xa protection from inactivation by antithrombin III have a rather low optimum concentration range, beyond which the original fast rate of inactivation tends to be restored. A direct interaction between antithrombin III and factor V or phospholipid was not found. Thus binding of factor V mediated by phospholipid and calcium ions, which brings about the increase in factor Xa proteolytic activity, also decreases the susceptibility of this enzyme to a biological inactivator in blood.     

Inactivation of ''Arvin'' by Plasma Proteins

S ummary The coagulant activity of Arvin is neutralized by incubation with normal human serum. Coagulation experiments, and chromatographic and electrophoretic studies using radioactive Arvin, indicate that Arvin interacts with at least two serum proteins. One of these is α₂ macroglobulin and the other may be antithrombin III. Although these proteins inactivate thrombin also, the mechanisms of neutralization of Arvin and thrombin are not identical. In addition, considerable amounts of radio-active Arvin are trapped in the fibrin mesh when fibrinogen is clotted with Arvin. Serum samples from patients clinically resistant to Arvin showed complexing of Arvin with a γ globulin fraction, confirming the antibody nature of Arvin resistance.     

奈替米星的临床研究

目的研究来替米星每日1次投药法治疗下呼吸道感染的临床效果、药代动力学、抗生素后效应和药物毒性。方法48例患者分为三组：（1）单一组14例,使用奈替米星,每天总量为6mg·kg-1·h-1;（2）合用组16例,使用头孢唑啉每12小时1次投药3g,奈替米星每天200mg;（3）对照组18例,使用头胞唑啉每12小时投药3g,与阿米卡星每天200mg联合使用,分别观察临床症状、实验室检查及临床疗效;应用荧光偏振分析仪（TDX）药物浓度自动分析仪研究其药代动力学;应用AVANTAGE生物分析仪研究奈替米星抗生素后效应,观察了奈替米星的肾、耳毒性。结果每日1次单用奈替米星组疗效较头抱叹批及阿米卡星组好。平均血药浓度为27．23mg／L谷浓度为0．23mg／L,半数药物消除相时间为5．095小时,药时曲线下面积为70μg·h-1·ml-1。奈替米皇0．5、1及4倍最低抑菌浓度（MIC）对4种细菌均显示不同程度的抗生素后效应。本组研究未发现耳、肾毒性。结论奈替米星每日1次投药法有较高血清浓度,较大药时曲线下面积,作为浓度依赖性杀菌药,此药临床效果较好,而且其抗生素后效应时间较长。