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Tina ★ India, 2013-04-20 09:09 (4812 d 23:45 ago) Posting: # 10442 Views: 9,574 |
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What is the difference between plasma half life and biological half life? If for a product the plasma half life is 3h while biological half life is 30h, do I need to consider biological half life for the wasout period? Considering differences in half life, will there be differences in the other PK parameters as well--biological Tmax! biological Cmax! biological AUC! What is the relation between Tmax and halflife? What are the properties of a product with lesser Tmax and higher half life and viceversa?  |
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ElMaestro ★★★ Denmark, 2013-04-20 22:53 (4812 d 10:01 ago) @ Tina Posting: # 10444 Views: 8,346 |
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Hi T., ❝ What is the difference between plasma half life and biological half life? I think what is meant is effect half-life? Only a guess. ❝ If for a product the plasma half life is 3h while biological half life is 30h, do I need to consider biological half life for the wasout period? If this is a compound that qualifies for PK-evaluation then I would say you can disregard effect considerations. ❝ Considering differences in half life, will there be differences in the other PK parameters as well--biological Tmax! biological Cmax! biological AUC! ❝ What is the relation between Tmax and halflife? What are the properties of a product with lesser Tmax and higher half life and viceversa? ❝ That stuff is complicated and it ultimately depends on the mechanism of action and ADME. For example, a Michaelis-Menten type of relationship between concentration and effect is often proven in vitro with some kind of easy assay but is very difficult to investigate in vivo. Throw in several receptors, various ED50-values and some biological variation and you quickly get data that is all over the place in view of the model. In the world of PK Tmax and Cmax are often taken as indicators of rate of absorption (which isn't always the same as rate of effect production) whereas AUC is an indocator of extent. "Biological Cmax" must be a misnomer?!? Tmax and half-life will typically not correlate meaningfully. — Pass or fail! ElMaestro |
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Tina ★ India, 2013-04-22 15:02 (4810 d 17:51 ago) @ ElMaestro Posting: # 10454 Views: 8,085 |
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Dear ElMaestro, Thank you for the reply. Does biological half life affect plasma concentration? What happens if a drug having greater tissue distribution redistributes to the plasma? Would not considering biological halflife not affect Cmax of period 2 (if redistribution occurs!)? Should we not assess the safety of the subjects throughout the wasout of the biological half life period? Thanks in advance for the guidance. Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut] |
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Rajdoc ☆ India, 2014-03-11 13:15 (4487 d 18:39 ago) @ Tina Posting: # 12591 Views: 7,112 |
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Dear Tina In such cases previous literature from the same studies would give an idea about the redistribution of drug into the plasma. In any case we check the pre dose concentrations in the second period which would give an idea about the left over concentrations. |
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Mahesh M ★ India, 2014-03-11 14:43 (4487 d 17:11 ago) @ Tina Posting: # 12595 Views: 7,216 |
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dear Tina, ❝ Does biological half life affect plasma concentration? There is two type of half life Alpha half life = plasma / distribution half life Beta half life = tissue / elimination half life Most of the drugs have alpha half life and remain in the plasma. Drugs having beta half life have two half lives, one in the plasma and one in the tissues. They are highly distributed drugs. Their total time of elimination is more. When the drug is absorbed and reaches the plasma, it is distributed to the tissues. Some drugs have high volume of distribution and are distributed to various tissues, mostly adipose tissue. More time is required for their elimination, thus have greater half life. What happens if a drug having greater tissue distribution redistributes to the plasma? Would not considering biological halflife not affect Cmax of period 2 (if redistribution occurs!)? Highly lipid soluble drugs given by intravenous or inhalation routes are initially distributed to organs with high blood flow. Later, less vascular but more bulky tissues (such as muscle and fat) take up the drug—plasma concentration falls and the drug is withdrawn from these sites. If the site of action of the drug was in one of the highly perfused organs, redistribution results in termination of the drug action. The greater the lipid solubility of the drug, the faster its redistribution will be. Regards Mahesh |
Ing. Helmut Schütz