ADME

ADME ، هو عبارة عن مختصر في الحرائك الفارماكولوجية (الدوائية) وعلم الأدوية للامتصاص الادوية '''a'''bsorption, وتوزعها '''d'''istribution، واستقلابها'''m'''etabolism، وإطراحها'''e'''xcretion وهذا المصطلح مكون من الأحرف الأولى من الكلمات الأربع السابقة. ويصف هذا المصطلح تصرف المركبات الكيميائية الصيدلانية داخل العضوية أن المعايير الاربعة تؤثر على مستويات الادوية وحركيتها وذلك للأدوية التي تتوضع في الانسجة وبالتالي تؤثر على أداء وفعالية الدوائية للمركبات كالادوية. ‏

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Criteria

أمتصاص/أعطاء ‏‎

‏‎ ‎للمركبات التي يجب ان تصل الى الانسجة عادة يجب ان تؤخذ في مجرى الدم (اي حقنا) .ولكن غالبا ليصل الدواء الى مجرى الدم يجب ان يعبر غشاء مخاطيا مثل غشاء السبيل الهضمي في الامتصاص المعوي‎-‎‏ ‏‎ after being taken up by the target cells. This can be a serious problem at some natural barriers like the blood-brainbarrier. Factors such as poor compound solubility, gastric emptying time, intestinal transit time, chemical instability in the stomach, and inability to permeate the intestinal wall can all reduce the extent to which a drug is absorbed after oral administration. Absorption critically determines the compound's bioavailability. Drugs that absorb poorly when taken orally must be administered in some less desirable way, like [[intravenous therapy|intravenously]] or by inhalation (e.g. zanamivir).

توزع الدواء

وهو عبارة عن حمل المركب الدوائي إلى المكان الهدف (مكان ظهور الفعالية المطلوبة)، وغالبا يتم توزع الدواء عبر الدوران الدموي. From there, the compound may distribute into tissues and organs, usually to differing extents. After entry into the systemic circulation, either by intravascular injection or by absorption from any of the various extracellular sites the drug is subjected to a number of process called as distribution process that tend to lower its plasma concentration.

Distribution is defined as the reversible transfer of a drug between one compartment to another. Some factors affecting distribution include blood flow rates and the drug binding to serum proteins forming a complex.

الاستقلاب

Compounds begin to break down as soon as they enter the body. The majority of small-molecule drug metabolism is carried out in the liver by redox enzymes, termed cytochrome P450 enzymes. As metabolism occurs, the initial (parent) compound is converted to new compounds called metabolites. When metabolites are pharmacologically inert, metabolism deactivates the administered dose of parent drug and this usually reduces the effects on the body. Metabolites may also be pharmacologically active, sometimes more so than the parent drug.

Excretion/Elimination

Compounds and their metabolites need to be removed from the body via excretion, usually through the kidneys (urine) or in the feces. Unless excretion is complete, accumulation of foreign substances can adversely affect normal metabolism.

There are three sites where drug excretion occurs. The kidney is the most important site and it is where products are excreted through urine. Biliary excretion or fecal excretion is the process that initiates in the liver and passes through to the gut until the products are finally excreted along with waste products or feces. The last method of excretion is through the lungs e.g. anesthetic gases.

Excretion of drugs by the kidney involves 3 main mechanisms:

  • Glomerular filtration of unbound drug.
  • Active secretion of (free & protein-bound) drug by transporters e.g. anions such as urate, penicillin, glucuronide, sulfate conjugates) or cations such as choline, histamine.
  • Filtrate 100-fold concentrated in tubules for a favorable concentration gradient so that it may be reabsorbed by passive diffusion and passed out through the urine.

Toxicity

Sometimes, the potential or real toxicity of the compound is taken into account (ADME-Tox or ADMET). When the Liberation of the substance (from protective coating, or other excipients) is considered, we speak of LADME.

Computational chemists try to predict the ADME-Tox qualities of compounds through methods like QSPR or QSAR.


The route of administration critically influences ADME.


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انظر أيضا

المراجع

  • {{cite journal | author = S.K. Balani; G.T. Miwa; L.S. Gan; J.T. Wu; F.W. Lee | title = Strategy of utilizing in vitro and in vivo ADME tools for lead optimization and drug candidate selection | journal = Curr Top Med Chem | year = 200

قالب:بذرة كيمياء صيدلية