Dear pharmacokinetics,Back to the Top
I am a young doctor (M.D. Pharmacology), I had just completed my
P.G., During surfing on net I found a letter from
dabhijit.at.cheminor.com asking for value of therapeutic index to you .
Dear as far as i know Therapeutic index(TI) is a ratio of LD 50 and
ED 50, But in certain literatures i found that Therapeutic index is
Cmax/Mic. So kindly tell me how this TI is calculated by knowing the
Cmax and MIC of the drug for perticular antibiotics. pls reply as soon
as possible. waiting for ur kind reply.
Dr KamleshBack to the Top
"ratio of LD 50 and ED 50, But in certain literatures i found
that Therapeutic index is Cmax/Mic. So kindly tell me how"
Cmax:MIC is not a therapeutic index.
I hope this helps.
(There are plenty of archives about what is a therapeutic index from
School of Pharmacy
University of Queensland
Tel +61 7 3365 8808
Fax +61 7 3365 1688
University Provider Number: 00025B
MCMC PK example: http://www.uq.edu.au/pharmacy/sduffull/MCMC_eg.htm
Dear Dr. KamleshBack to the Top
Therapetic index is the ratio of the dose required to produce toxic or
lethal effects to dose required to produce nonadverse or therapeutic
response.(ratio of LD 50 and ED 50)
Regarding Cmx/MIC here is the explanation:
After 60 years of antibiotic treatment, attempts to rationalize it have
culminated in the use of pharmacological indices. These indices
facilitate comparison of the activity of different antibiotics and
serve as a sound basis for antibiotic dosing. Pharmacokinetic
parameters (e.g. AUC, Cmax) and pharmacodynamic parameters (mostly MIC)
are used for this purpose. For the so-called concentration-dependent
antibiotics, the pharmacological indices AUC/MIC and Cmax/MIC are used,
whereas for time-dependent antibiotics, the pharmacological index T>MIC
is used. Some authors believe that the index AUC/MIC can be used as a
universal index, but, not all experts accept this generalization. As
the various pharmacological indices have been defined inconsistently in
the literature, the International Society for Anti-Infective
Pharmacology (ISAP) has published a paper on the terminology of
pharmacokinetic and pharmacodynamic parameters and the pharmacological
indices. This paper will help to
ensure uniform use of terminology.
Also I will suggest you to see this Discussion paper (Points to
Consider) presented by the European Agency for the Evaluation of
Medicinal Products (EMEA, London, UK) - released: December 16, 1999.
DR.Sajjad A. Desai
Dear allBack to the Top
Dr Kamesh wrote "in certain literatures I found that Therapeutic Index
This index started as a clinical concept especially relevant to drugs
digoxin that has an uncomfortably low therapeutic index (around 2 to 3)
combined with a marked tendency to accumulate due to relatively slow
elimination. In the 1970s the ratio ED50/LD50 was a useful new way to
it in toxicological terms. Using Cmax/MEC50 is another step along that
pathway but I'm not at all sure that it works as well as the
method because Cmax is such a short-lived and changeable item. It
the discussion going on in the forum about AUC and efficacy in cancer.
If I had to choose a ratio related to Pk I think I would favour a
toxic AUC24hrs/Minimal Effective AUC24hrs, though I can also see a good
logic for different periods of time.
Andrew Sutton, MBBS, MD(London), FFA
Guildford Clinical Pharmacology Ltd.
Hascombe Ward, Royal Surrey County Hospital,
Guildford, Surrey GU2 7YXX, UK
Tel: +44 (0)1483 406886
There are lots of ways to define this. One good one is the minimumBack to the Top
plasma concentration producing the desired effect divided by the
minimum plasma concentration causing toxicity. One could also use the
means/medians of ranges producing these effects. For example,
phenytoin is active between 10-20 mcg/mL, with mild toxicity at 20-30
mcg/mL. The TI is therefore somewhere in the vicinity of 2 or
thereabouts. Best wishes. Harold.
Harold Boxenbaum, Ph.D.
14621 Settlers Landing Way
North Potomac, MD 20878-4305
The ratio describe by Harold is actually the minimum concentrationBack to the Top
producing toxicity divided by the minimum effective concentration.
Drugs exhibiting values of this ratio around 2 or less are usually
considered highly toxic.
Radu D. Pop
Vice President, Scientific Affairs
Pharma Medica Research Inc.
966 Pantera Drive
Canada, L4W 2S1
Dear Harold,Back to the Top
I did not get u'r logic here. Do you mean to say that MTC/MEC or MEC/MTC?
As per my knowledge it is Minimum Toxic Conc/Minimum effective conc. I
am sorry if I am misunderstanding your statement here.
KANTHI KIRAN V.S. VARANASI, M.Pharm, MBA
Sr. Research Scientist,
Drug Metabolism and Pharmacokinetics Department,
Glenmark Pharmaceuticals LTD.
Glenmark Research Centre,
Plot No. A-607, T.T.C Industrial Area,
Ph.: 91-22-55902491/92 ext 315
Kanthi,Back to the Top
You can do it a number of ways, as long as you define how you do it.
Using the ratio you described is one way, probably the most popular and
widely used. In the case of phenytoin, the therapeutic region is 10-20
mcg/mL, and one sees minor toxicity at 20-30 mcg/mL. So you can take
25/15, or 20/10, so long as you define how you are making your
calculation. But the minimum toxic conc over the minimum therapeutic
conc is the most usual. Best wishes. Harold.
In the context of your question, its MTC/MEC. Harold.Back to the Top
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