Subject biological half-life

In the foregoing example, the drug was administered to a healthy subject who had normal kidney and liver function. The estimated biological half-life in this... 

When individuals were administered 800 mg. per day of phenylbutazone (Butazolidin) for 14 days or more, each developed a characteristic plasma level.39 For 60 subjects this level ranged from 60 to 150 mg. per liter and was constant from day to day for individuals. It was concluded that the rate at which the drug was metabolized under the conditions used varied from 17 to 35 per cent per day for different individuals. It is interesting that the "biological half-life" of this substance varies from species to species3 hours for rabbits, 6 hours for dogs and rats, 72 hours for man. It is also clear from the above that its rate of disappearance varies widely for individual human subjects. 

Metabolism/Excretion- In healthy subjects, the half-life of pramlintide is approximately 48 minutes. Pramlintide is metabolized primarily by the kidneys. Des-lys pramlintide (2-37 pramlintide), the primary metabolite, has a similar half-life and is biologically active both in vitro and in vivo in rats. AUC values are relatively constant with repeat dosing, indicating no bioaccumulation. 

Appendix B reviews some important animal studies of cholinesterase reactivator chemicals. The extensive literature reviewed offers little definitive information with which to project possible long-term effects or delayed sequelae in human subjects tested at Edgewood. These compounds have a short biologic half-life of 1 to 3 h. However, no chronic studies were found. Consequently, the carcinogenic potential of cholinesterase reactivators remains... 

Measurements of activity in blood of seven subjects were continued for 14 d after inhalation and showed that lead was lost from blood with a biological half-life of 18.0 (s.e.) 0.9 d. Because of radioactive decay, it was not possible to continue measurements for a longer period. Rabinowitz et al. (1976) gave oral doses of the stable lead isotope 204Pb to four subjects daily for several months, and used mass spectrometry to measure 204Pb in blood. The decline in 204Pb in blood was found to be exponential over periods of about 100 d from the end of the period of... 

The total body pool of folate in adults is 17 ixmo (7.5 mg), with a biological half-life of 101 days. This suggests a minimum requirement for replacement of 85 nmol (37 /xg) per day (Herbert, 1987a). Studies of the urinary excretion of acetamido-p-aminobenzoyl glutamate in subjects maintained on folate-free diets suggest that there is catabolism of 170 nmol (80 /xg) of folate per day. 

After intravenous administration of a tracer dose of thallous-201 chloride, the cation disappears quickly from the circulation, with a biological half-life in the blood of less than 1 min, as the T1 is rapidly taken up by different tissues, especially heart and skeletal muscle (Kazantzis, 1986 Pennal et al., 1992). In apparently healthy individuals subjected to standardised physical exercise on a bicycle ergometer before intravenous administration of T1 chloride (80 MBq), it was found that 3.9% of the... 

The bioavailability of molecules exclusively screened through in vitro assays can be low. Because of the polarity of the functional groups present in the molecule, they may be poorly absorbed or incorrectly distributed. They may also, as a result of their vulnerability, be the subject of early metabolic destructions, such as first-pass effects or any other kind of degradation leading to a short biological half-life. For such molecules, in vivo administration is limited to the parenteral route, and their clinical usefulness is thus restricted. Sometimes an adequate pharmaceutical formulation (micro-encapsulation, sustained-release or entero-soluble preparations) can overcome these drawbacks, but often the galenic formulation is inoperant, and a chemical... 

Vitamin Bj2 deficiency gives rise to pernicious anemia. However, due to the small amounts required for the maintenance of health (3.5 pg per day per adult), genuine dietary deficiencies develop rarely, for example in strict vegetarians. Even in subjects with diminished or absent IE production, the first symptoms of vitamin Bj2 deficiency appear only in the fourth decade of life, due mainly to the long biological half-life of the... 

Subject no. Biological half-life (days) (7 (days) Uptake (HML) (%) Uptake (H) (%)... 

Table 18.3 shows that the average biological half-life of the subjects with intact thyroid glands is 66.1 6.3 days. This moderate decrease in biological half-life of the North American group that participated in this study from ICRP values is a continuation of the trend identified above. 

While widely used, this procedure is subject to several difficulties and limitations, (a) It allows introduction of only one type of ligand, or one distribution of ligands, into the technetium radiopharmaceuticaL (b) It does not allow specific control over the final oxidation state, coordination number, coordination geometry, etc. of the technetium in the Tc-L product, (c) The reductant, especially Sn, is often incorporated into the final product (1,6). (d) The excess reductant is injected into the patient tindl) has a long biological half-life (7) and causes several deleterious side effects (8). 

Labelled bicarbonate on its own can be used to assess EE instead of doubly labelled water. This technique is valuable for short intervals of about 1-3 days because of the shorter biological half life of bicarbonate compared with water. It is applicable to humans only, if stable marked bicarbonate (NaH CO,) is used. This substance is less expensive than doubly labelled water, but relies like DLW on the quite expensive technology of IRMS. The bicarbonate is con.stant-ly infused and will reach rapidly an equilibrium with the CO2-P00I of the subject s body. COj-production will dilute this pool. The CO production rate can be calculated from the variations in the dilution of labelled COj and the infusion rate. The method assumes no isotope exchange or fixation and a constant pool of bicarbonate. It is not as accurate as the doubly labelled water method Elia [39] found individual accuracies of up to 6%, validated against whole body calorimetry in a calorimetric chamber. 

Human subjects suffering from myasthenia gravis have received daily doses of 25 mg. for 3 months with beneficial results and no toxic symptoms. Under neutral conditions it is estimated2 that the half-life in water is some 100 years. Hydrolysis is catalysed by acids with fission of a N—P link and the half-life in normal acid is 200 min. Hydrolysis is catalysed by alkali with fission of the POP link the half-life in n sodium hydroxide is 70 days. At biological pH it would appear that it should be indefinitely stable, but as we shall see, other factors besides pH must be taken into account in biological systems. 

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