Steroid Half-Life

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Steroid Half-Life

Steroid Half-Life


Understanding Drug Half-Lives

by William Llewellyn

There are a number of factors that can affect the potency of a particular drug compound. One such factor, and perhaps one of the most important, is the half-life of the agent. In medicine, the term half-life refers to the duration it takes for half of a given drug dosage to break down in the body. It is not half of the total activity time, as this figure always refers to the time it takes to metabolize 50% of what is in still the body. For example, if we inject 100mg a steroid with a half-life of 4 hours, at the four-hour mark we should have only 50mg left as active. After another four hours have passed the drug is still in the body, however another half-life has expired and the total active dosage will be around 25mg. It may take several half-lives before the drug is completely inactive.

A good way to illustrate half-life is through the "flipping penny" experiment. I remember it well from my high school earth sciences class, and I'm sure many of you have probably done this exercise as well. This experiment involves placing 100 pennies inside a flat, closeable box. It is big enough that the pennies can sit side by side comfortably without overlapping each other. We begin with them all facing "heads-up". Next we close the box, give it a good shake, and then open it back up again. We then proceed to remove all pennies that are now "tails-up" in the box. This process is repeated until all of the pennies have been flipped and are removed from the box. We find that with each shake we loose about half of them. Around 50 the first flip, 25 the second, a dozen of so on the third, and so on. Although half of the original amount are tailed and removed on the first flip, it takes many successive tries to clear them all. And usually there are a couple of kids in the class that just can't seem to get the last few over without a lot of work. This illustrates well the way in which we measure drug metabolism in the body. Half-life is not an easy reference for the total time a drug will be found active in the body, but more a guide to optimizing a dosing schedule and avoiding unwanted peaks and troughs.

Unaided Steroid Half-Life

In the early years of steroid research, half-life was one of the biggest roadblocks to the development of commercial compounds. Natural steroid hormones have very short half-lives, which can make maintaining a normal blood level very difficult. For example, the half-life of free testosterone in the blood is only a few minutes (1), and from the site of injection it is well short of one hour. It is also so easily processed by the liver, that when you take it orally only a tiny fraction will actually be intact by the time it reaches the blood. With the oral route too difficult, repeated regular injections would probably be the only option to use testosterone for therapy at all. Obviously this is extremely tedious and uncomfortable to do, which led scientists to focus closely on ways to extend the life of this and other hormones in the body. Lets take a close look at the two most popular methods that were developed and ultimately adopted by the pharmaceutical industry for extending steroid half-life.

Oral 17alpha alkylation

You have most lively seen this reference in steroid materials. 17alpha alkylation is a process in which an extra carbon atom is added to the steroid molecule at the 17th position. This atom occupies a bond needed for the steroid to reduce to inactive 17-keto form, totally inhibiting this pathway of metabolism (2). The addition of 17 alkylation works to extend the half-life of the steroid considerably. With it we present we have half-lives measured in hours instead of only minutes. Unfortunately 17alpha alkylation also can lessen the ability of the steroid to bind to the androgen receptor. But the two traits balance out such that typically we still have a more physiologically active steroid molecule though (3). This alteration is the most favorable for oral dosing. Since the liver cannot process this type of steroid well, a large percentage will make it to the blood stream intact. It however is also somewhat toxic to the liver, and therefore less than ideal, especially if we are considering another avenue of administration such as injection.

Esterification for Injection

Most injectable steroid compounds utilize esters to increase their half-lives in the body. Esterification is a process where a carboxylic (fatty) acid is attached to the steroid molecule at the 17th beta position. One purpose of this is to protect its active 17-hydroxyl group. It is a prime target of steroid metabolism, and with the ester present this is prevented. The ester also makes the steroid compound more oil soluble. This makes it more difficult for the blood to pick it up and carry it into circulation, and likewise slows the rate the drug can leave the injection site. As a result, an inactive deposit of steroid can sit at the site of injection, releasing slowly for days or weeks into the blood stream. Once free in the blood the ester is removed quickly by enzymes, and the base steroid is rendered active.

We can look at the half-life of injectable compounds in two ways. The first is the half-life for the release of the steroid from the injection site. This is usually measured in days with most commercial steroid preparations. In fact the total active lifespan of most oil-based esterified injectables is measured in weeks, sometimes several weeks. The second measure is to look at its half-life in open blood circulation. This is more a figure for personal interest sake than any practical application however, as the only relevant measure to the user is its release half-life. In any event, we can look at a human injection study with nandrolone decanoate (Deca) and see some pretty accurate figures on both measures (4). First we find that Deca exhibits a mean half-life of 6 days for the release of steroid from the injection site. You can see why people say that Deca can technically be active for as long as a month after injection. Next we find a half-live of about 4 hours for the hydrolysis of serum nandrolone decanoate to free nandrolone, and the total distribution and metabolism of nandrolone. The half-life for simply the removal of the decanoate ester was about an hour or less. Provided in the chart below as well are the relative half-lives of nandrolone and two other esters of it from intramuscular injection depot (5).

Compound Half-Life

Nandrolone 30-40 minutes
Nandrolone phenylpropionate 1 day
Nandrolone decanoate 6 days
Nandrolone laurate 10 Days



References
1- Metabolism of Anabolic Androgenic steroids. V. Rogozkin. 1991 CRC press.
2 - Metabolism of synthetic steroids. Fotherby K, James F. Adv. Steroid biochem pharmacol 1972 3: 67-165.
3- Binding of 17-a-methyltestosterone in vitro… Wiita, Artis, Ackerman and Longcope. Therapeutic Drug Monitoring. 17(4) 377-80
4- Pharmacokinetic parameters of nandrolone (19-nortestosterone) after intramuscular administration of nandrolone decanoate to healthy volunteers. Wijnand, Bosch and Donker. Acta Endocrinol 1985 (suppl 271) 19-30
5- Implications of basic pharmacology in the therapy with esters of nandrolone. Acta endocrinol 1985 (suppl 271) 38-43




















Steroid Half-Life

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Aldactone (Spironolactone)
Anadrol
Anadur
Anavar
Andriol
AndroGel
Arimidex (Anastrozole)
Bromocriptine
Clenbuterol
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Cytadren
Danatrol
Danocrine
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Dianabol
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Equipoise
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Esiclene
Finaplix
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HGH (Human Growth Hormone)
How To Inject Steroids
Insulin
Lasix
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Masteron
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Metribolone
Miotolan
Nilevar
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Sustanon 250
Teslac
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Testosterone Suspension
Winstrol Depot (Stromba)
Aldactone (spironolactone)
ANADROL (A50) - Oxymethylone
ANADUR - (nandrolone hexyloxyphenylpropionate)
ANAPOLAN
ANAVAR - OXANDRALONE
ANDRIOL- testosterone undecanoate
ANDRODERM
Androgel - Testosterone Gel
ANDROSTANOLONE
ARATEST-250-500-2500
Arimidex - Anastrozole - Liquidex
Aromasin - exemestane
Catapres - Clonidine hydrochloride
Cheque Drops
CLENBUTEROL HYDROCLORIDE
CLOMID- clomiphene citrate
CYCLOFENIL
CYTADREN - aminoglutethimide
CYTOMEL T-3
DANOCRINE- danazol
DECA Durabolin - nandrolone decanoate
DIANABOL - Dbol - methandrostenlone / methandienone
DNP - (2,4-Dinitrophenol)
Durabolin - Nandrolone phenylpropionate
Dyazide
DYNABOLAN
EPHEDRINE
EQUIPOISE - EQ - boldenone undecylenate
TESTOSTERONE CYPIONATE
TESTOSTERONE ENANTHATE
Erythropoietin - EPO, Epogen
ESCICLINE - formebolone
ESTANDRON
  Femara - Letozole
FINAPLIX - trenbolone acetate
HALOTESTIN - fluoxymesteron
HGH - HUMAN GROWTH HORMONE
Human Chorionic Gonadotropin (HCG)
INSULIN
L-THYROXINE-T-4/liothyronine sodium
LASIX - Furosemide
LAURABOLIN - nandrolone laurate
MASTERON
Megagrisevit Mono - Clostebol acetate
MENT - MENT, 7 MENT, Trestolone acetate
METHANDRIOL - methylandrostenediol dipropionate
METHYLTESTOSTERONE
MIOTOLAN - furazabol
NAXEN - naproxen
NELIVAR - norethandrolone
NOLVADEX - tamoxifen citrate
NUBIAN
OMNADREN-250
ORABOLIN
TESTOSTERONE HEPTYLATE
PARABOLAN - trenbolone hexahydrobencylcarbonate
Primobolan Acetate
Primobolan Depot
Primoteston Depot
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TESTOVIRON
WINSTROL DEPOT - stanazolol (INJECTABLES)
WINSTROL - stanazolol (oral)
Anabolicurn Vister (quinbolone)

Steroid Half-Life

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Steroid Half-Life
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