Half life of elimination

Another important storage depot for toxic compounds is the skeleton. In particular, cadmium and lead bind and accumulate in the bone tissue from which they are released very slowly. The half-life of elimination of cadmium is several years, the half-life of lead is several months. 

It is not metabolized by the liver, but is primarily excreted unchanged in the urine (half-life of elimination = 60 to 80 hours). 

When a preparation of phenytoin was administered to a patient, the volume of distribution was found to be 70 liters, and the half-life of elimination was 1.5 hours. What is the total clearance of phenytoin ... 

In switching drugs, the half-life of elimination that is being stopped should be considered if drug interactions are to be avoided. The time taken for the withdrawal of a drug depends on the duration of treatment sedatives, antiepileptics and anxiolytics may take several weeks to withdraw. 

In the case of drugs renally eliminated in unchanged form, the half-life of elimination can be calculated from the cumulative excretion in urine the final total amount eliminated corresponds to the amount absorbed. 

Metabolism/Excretion - Ipratropium is partially metabolized to inactive products. The half-life of elimination is about 2 hours after inhalation, nasal, or IV administration. 

Although benzodiazepine dependence is very common, cases that fulfill all the diagnostic criteria for addiction are rare. Withdrawal from benzodiazepines occurs within days of stopping the medication and varies as a function of the half-life of elimination. Symptoms include irritability, insomnia, phono- and photophobia, depression, muscle cramps, and even seizures. Typically, these symptoms taper off within 1-2 weeks. 

In species where reabsorption of drugs from the gastrointestinal tract increases the half-life of elimination, salivary secretion represents another important excretion route. The large volume of alkaline saliva produced by ruminants offers the possibility of trapping the acidic drugs. Exhalation of products of drug metabolism, such as carbon dioxide and water, can also account for drug excretion. 

Tetrahydrocannabinol is metabolized in the liver to form active metabolites which are further metabolized to inactive polar compounds these are excreted in the urine. Some metabolites are excreted into the bile and then recycled via the enterohepatic circulation. Because of their high lipophilicity, most active metabolites are widely distributed in fat deposits and the brain, from which sources they are only slowly eliminated. The half-life of elimination for many of the active metabolites has been calculated to be approximately 30 hours. Accordingly, accumulation occurs with regular, chronic dosing. Traces of the cannabinoids can be detected in the blood and urine of users for many days after the last administration. There is some evidence of metabolic tolerance occurring after chronic use of the drug. THC and related cannabinoids readily penetrate the placental barrier and may possibly detrimentally affect foetal development. 

After the photosensitizer is administered intravenously it accumulates in areas of the disease and is eliminated from the circulation over a time course that varies from compound to compound. So, in addition to choice of the drug dose and light dose, another important variable is the time from drug administration to light activation. This time is called the DU (discussed in an earlier section). With drugs that accumulate slowly in plaque and/or have a long half-life of elimination... 

An estimate of the half-life of elimination from plasma has been reported in humans. Uptake of potassium dichromate was determined in a man who was given 0.8 mg of chromium(VI) in drinking... 

Gaur and Chandra23 extended their earlier studies in mice with 14C-tilorone. Following an intraperitoneal injection of 20 mg/kg in male AKR-mice, the half-life of elimination was about 72 hr with the major excretory route by way of the kidney. In confirmation of earlier findings, spleen and kidney had the highest specific activity. Distribution of radioactivity 24 hr after the dose was liver, 25% spleen, 2.5% kidney, 2.3% lungs and pancreas, about 1.5% each and less than 0.5% of the administered dose in each of the remaining tissues. 

These are both negative chronotropes and positive inotropes, and have a narrow therapeutic index and relatively long-half life of elimination (digoxin 14-60 hours, digitoxin 30-40 hours). 

If tolerance develops, the short half-life of elimination may result in increased anxiety during the day and/or increased wakefulness during the latter part of the night... 

Relevant kinetic parameters (half-life, body pool, and mean transit time in organs) can be calculated. According to Equation 1 the specific activity in plasma shows a triphasic decay with half-lives of ti = 1.1 h, t2 == 22 h, and 3 == 61 h. The half-lives ti and 2 essentially describe the distribution of the compound into the system. The third half-life of 61 h (2.5 d) is valid for all tissues after attainment of the distribution equilibrium and represents the overall half-life of elimination from the body under the special conditions of the study (ascorbate status of the animals). 

Indinavir. When administered with a high fai diet, indinavir (Crixivan) achieves a maximum serum concentration of V< ul the administered dose. The drug is 60% bound in the plasma. It is extensively metabolized by CYP 3A4, and seven metabolites have been identified. Oral bioavail-abiiity is good, with a of 0.8 0.3 hour. The half-life of elimination is 1.8 hour, nnd the elimination products are delectable in feces and urine. Indinavir also causes dyslipide-mm. The available dosage forms are capsules of 200, 333, and dOO mg. 

The apparent half-life of elimination is 5-10 h. The primary route of elimination is via the kidneys. 

Diazoxide is well absorbed orally. It is distributed to the plasma where it is highly bound (>90%) to the plasma proteins. It readily crosses both the placental and blood brain barriers. The volume of distribution is 180 ml kg The half-life of elimination for diazoxide is 15-30 h. Approximately 20-50% of diazoxide is eliminated unchanged by the kidney, with the remainder being metabolized by the liver to 3-carboxy and 3-hydroxymethyl derivatives. 

Half-life of elimination (ti/2) This is the time period (e.g., minutes, hours, and days) during which the blood concentration of a xenobiotic falls to one-half of its original value as a result of all processes of distribution, biotransformation, and excretion. The determination of ti/2 is based on the calculation of the elimination rate constant described above (/c) ... 

The respiratory half-life for elimination of PERC has been estimated at 65-70 h and is a result of the very slow elimination of PERC from fat stores. The half-life of elimination of trichloro metabolites of PERC is estimated as being 144 h. This long half-life of elimination has serious implications with regard to the accumulation of PERC during chronic or multiple exposure situations. 

Abstract Metabolism and kinetic studies have shown that the overall elimination of ETBE and MTBE from blood in volunteers was multiphasic, (two or four phases in the case of ETBE and two or three phases for MTBE). The half-lives varied in different experiments and ranged from a few minutes for early phases up to a terminal half-life of 33 h in one experiment each with ETBE and MTBE. The kinetic data obtained from experiments with rats exposed to ETBE are restricted to a statement that the apparent half-life of elimination of ETBE from blood is about 0.8 h, but it is not clear if this only refers to an initial half-life. Some guidance may be possible from the known behaviour of MTBE. Its elimination from rat blood appears to be biphasic, with an initial half-life of less than 1 h and second half-lives ranging from 37 h to 92 h (reviewed in McGregor 2006). Elimination occurs in exhaled air (mainly unchanged ethers) and urine (metabolites). 

Half-life of elimination appears to increase when the exposure time was shortened from 8 to 4 min, while the exposure concentration is increased two-fold. Apparently, such a phenomenon seems hard to understand. The calculated elimination half-Ufe would probably be appreciably longer if a data point at 60 min would be available. 

As in all instantaneous absorption models, the entire absorbed dose of drug is taken to enter the systemic circulation instandy at time zero (< = 0). This provides an excellent approximation of the rapid drug delivery direcdy into the systemic circulation provided by a bolus IV injection, which truly occurs over a very short period of time (typically several seconds). However, this assumption does not actually require a strict interpretation of the word instantaneous. Even if an absorption process takes a substantial period of time (minutes or hours), it can still be approximated as instantaneous as long as absorption occurs quickly relative to other ADME processes. Thus, other routes of drug delivery besides a bolus IV injection can be approximated by instantaneous absorption if the time it takes for the absorption process to be essentially complete is very small compared to the half-life of elimination. The equations throughout most of this section are written specifically for a bolus IV injection, but modifications that can be employed to apply the equations to other drug delivery methods are described in Section 10.7.5. 

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