Chemotherapeutic index

Similarly Magidson et al., in a series of 6-methoxyquinolines substituted at C by the chain. NH—[CHjJn—NEtj found in anti-malarial tests in siskins, the following changes in the chemotherapeutic index — ... 

Ehrlich was keenly aware of the need for safe and effective pharmaceuticals. Among his many other contributions to the field of pharmacology, Ehrlich developed the idea of a chemotherapeutic index. Ehrlich defined chemotherapeutic index as the minimum curative dose divided by the maximum tolerated dose (Equation 1.1). 

Ehrlich provided a quantitative measure to accompany the concept that a therapeutic dose must be evaluated relative to a toxic dose. Although Ehrlich s chemotherapeutic index has been displaced by more precise measures of effectiveness and toxicity, the spirit of Equation 1.1 remains a central idea of modern drug discovery. Ehrlich s work in the field of medicine, especially in the area of autoimmune disorders, resulted in his sharing of the Nobel Prize in Medicine in 1908. 

Determination and cataloging of the chemotherapeutic index of the 600 compounds Ehrlich and Hata synthesized enabled them in 1909 to discover arsphe-mamine (Salvarsan). This drug was very toxic but safer than the then currently used Atoxyl. It was used up to the mid-1940s, when it was replaced by penicillin. 

Today, Ehrlich s chemotherapeutic index has been updated to take into account the variability of individuals and is now defined as its reciprocal, the therapeutic index or ratio ... 

The 8-aminoquinolines were the first synthetic antimalar-ial drugs to be introduced into medicine. Pamaquine (Plasmochin) was the first to be marketed in 1926, but primaquine proved to have the highest chemotherapeutic index of the many compounds tested. 

Extracts of various Sophora species have earlier been reported to show antitumour activity, and it was therefore of interest to determine which, if any, of the alkaloidal constituents was responsible for this activity. Kojima et al.21 have now shown that matrine exhibits anti-tumour activity against Ehrlich ascites tumour in mice, and both matrine and matrine N-oxide show activity against solid Sarcoma-180 in mice. In fact, the chemotherapeutic index of matrine IV-oxide for Sarcoma-180 is estimated to be about 7.8 times that of mitomycin C. 

A measured quantity of the test compound is administered by various routes. From the activity in vivo the value of EDjq is calculated. The chemotherapeutic index is determined from the ED 50 and LDjp, which assesses the final therapeutic value of nitrofurans. 

The drug is an isomer of primaquine, has been studied extensively by Russian researchers. It has been used widely in the Eastern Europe, but despite claims to the contrary its chemotherapeutic index is appreciably lower in comparison to primaquine. ... 

A series of amidino ureas synthesised in Poland, and exemplified by nitro-guanil (78), were introduced as substitutes for proguanil because of their more favourable chemotherapeutic index [275, 276]. Although proguanil is... 

Chemotherapeutic drugs available before 1935. The chemotherapeutic index. 214... 

In seeking drugs which would have a great affinity for the invader and little for the host, Ehrlich introduced the Chemotherapeutic Index which he defined as the ratio ... 

---