Drug Properties Absorption Distribution And Elimination Phases

Detection of a drug depends largely on its absorption, distribution, and elimination properties. There are various routes of drug administration; oral (e.g., drinking ALCOHOL or swallowing pills), intravenous (e.g., HEROIN injected into a vein) and inhalation (e.g., smoking MARIJUANA; snorting COCAINE; sniffing GLUE). Drugs taken orally are usually the slowest to be absorbed (i.e. the speed at which the drug reaches the brain and other body organs) whereas intravenous and inhalation routes result in the fastest absorption. Once the absorbed drug enters the blood stream it is rapidly distributed to the various tissues in the body. The amount of drug stored depends on the nature of the drug, the quantity, duration of ingestion, the tissue holding the drug and the frequency of use.

Some drugs are fat-soluble and are deposited in fat tissues. For example, S9-TETRAHYDRO-CANNABINOL (THC), the active ingredient in marijuana, is highly fat-soluble, resulting in rapid reductions in blood levels as the drug is being distributed to the various tissues. Blood levels of S9-THC peak and start to decline in half the time it takes to smoke a marijuana ''joint.'' Concentrations are known to fall by almost 90 per cent in the first hour. Depending on the amount of drug stored in the fat tissues, detection may be possible in the urine for many days after last use. There are cases where marijuana metabolites have been detected for as long as sixty days after last use, since small amounts from fat go back into blood and appear in the urine. Ethanol or ethyl alcohol (the beverage alcohol) is not fat-soluble but is distributed in the total body water. Since blood is mostly made up of water, the presence of alcohol is easier to detect than fat-soluble drugs like S9-THC.

The ''absorption'' and ''distribution'' phases are followed by an ''elimination'' phase. The liver is the major detoxification centre in the body where the drugs are metabolized as blood circulates through this organ. The metabolites are then excreted into the urine through the kidneys. At the same time, drugs deposited in fat tissues are also slowly released into the blood stream and metabolized.

Small Intestine Glutamine Ammonia

A laboratory technician tests a urine sample for the presence of drugs, 1986. (© Ed Kashi/CORBIS)

Drugs vary by their elimination half-life. An elimination half-life is the amount of time needed for the drug level to fall by 50 percent. Every halflife the drug level falls by 50 percent. Table 1 shows the impact of the half-life on the amount of drug left in the body. At the end of 7 half-lives over 99 percent of the drug will be eliminated from the body. (See Table 2 for drug half-lives). The halflife of a drug is heavily influenced by a variety of factors including the individual's age, sex, physical condition as well as clinical status. A compromised liver and concurrent presence of another disease or drug have the potential of enhancing the toxic effects of the drug by slowing down the elimination process. Under different clinical conditions, how ever, this process may be speeded up. Therefore, great variation can be found in the half-lives of the same drug.

Approximately six half-lives are required to eliminate 99 per cent of any drug. Because cocaine's half-life is relatively short, averaging one hour, only six hours are needed for elimination of 99 per cent of the drug. On the other hand, cocaine's metabolites have a longer half-life and can be detected for a considerably longer period of time through urine drug assays. Compared to cocaine, PHENOBARBITAL has a much longer half-life of 80-120 hours, so that at least 480 hours (or 20 days) are required to eliminate 99 per cent of the drug. Since there is much variation in the half-life of different drugs and the absolute amount of drug present can be very small, it is crucial that the appropriate body fluid for analysis is selected for testing.

Ethanol is absorbed from the stomach by simple diffusion. Gastric absorption is fastest when strong drinks, distilled spirits containing 40 to 50 percent ethanol by volume are consumed. Dilute beverages, such as beer (4-5% ethanol) or wine (11-12% eth-anol) are absorbed slowly. Alcohol is absorbed very rapidly from the small intestines. The essential action of food is to delay gastric emptying and thus slowthe absorption process. Typically, studies have shown that peak BAC is reached between 30 minutes and 90 minutes of consumption; earlier on an empty stomach and later on a full stomach. Once absorbed, ethanol rapidly diffuses throughout the aqueous compartments of the body, going wherever water goes.

TABLE 1

Impact of Half-Life

TABLE 1

Impact of Half-Life

Start

Amount of drug left in the body

Amount of drug eliminated

100%

100%

End of 1st half-life

50.0%

50.0%

End of 2nd half-life

25.0%

75.0%

End of 3,d half-life

12.5%

87.5%

End of 4th half-life

6.25%

93.75%

End of 5th half-life

3.125%

96.87%

End of 6th half-life

1.56%

98.44%

End of 7th half-life

0.78%

Drug Half-Lives and Approximate Urine Detection Periods*

Drug

Half-life (t2)

Detection period

Methamphetamine Amphetamine (metabolite of methamphetamine)

Heroin

Morphine (metabolite of heroin)

6-Mono-acetyl-morphine (MAM)

Phencyclidine (PCP)

Cocaine

Benzoylecgonine (metabolite of cocaine)

^'-Tetrahydrocannabinol

ö9-Tetrahydrocannabinoic acid (marijuana metabolite in urine)

Benzodiazepines Diazepam

Flunitrazepam (rohypnol) Methadone

Barbiturate (phenobarbital) Alcohol (ethanol)

Gamma-hydroxybutyrate (GHB)

12-34 hours 7-34 hours

60-90 minutes 1.3-6.7 hours

30 minutes 7-16 hours 0.5-1.5 hours 5-7 hours

14-38 hours

Few hours to days

15-40 hours 9-25 hours

15-40 hours In chronic patients ~22-24 hours

35-120 hours

Blood levels fall by an average of 4-5 mmol/L/hour (15-18 mg/100 mL)/hour

2-3 days

In minutes Opiates positive for 2-4 days (EIA)

Few hours

2-3 days Few hours

3-5 days

90% fall in 1 hour

(blood) Depending on use, few days to many weeks days to weeks, depending on halflife 2 weeks 0.2% excreted unchanged!

1-2 weeks after last use

1.5 > 12 hours depending on the peak blood level. Urine typically positive for an additional 1-2 hour. Less than 12 hours

*The detection period is very much dose-dependent. The larger the dose, the longer the period the drug/metabolite can be detected in the urine

Absorption, distribution into different tissues and elimination are dynamic processes and take place simultaneously. The rate of removal of ethanol from the body is the sum of the rates of excretion in urine, breath and sweat, and the rate of the metabolism in the liver and other tissues. In humans, alcohol metabolism follows a "zero" order kinetics, i.e., it is largely independent of alcohol concentration in the blood and its levels decline almost linearly over time. The implication of this is that BAC falls at a constant rate over time. In social drinkers it is from 0.015 to 0.018 percent (15 mg/ 100mL to 18 mg/100mL) per hour and in heavy drinkers it is typically between 0.018 and 0.025

percent (18mg/100mL to 25mg/100mL) per hour. In the alcoholic patient, the elimination rate is generally higher. In forensic calculations, a rate of 0.015 percent (15mg/100mL) per hour is usually used. In our studies we have found 0.018 percent (18mg/100mL) per hour to be the average rate of metabolism. The larger the dose of alcohol given, the longer the duration of the measurable blood alcohol concentration.

Beat The Battle With The Bottle

Beat The Battle With The Bottle

Alcoholism is something that can't be formed in easy terms. Alcoholism as a whole refers to the circumstance whereby there's an obsession in man to keep ingesting beverages with alcohol content which is injurious to health. The circumstance of alcoholism doesn't let the person addicted have any command over ingestion despite being cognizant of the damaging consequences ensuing from it.

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