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Absorption, determination following oral administration

Preclinical Pharmacology. The pharmacokinetics of total and free platinum were determined following oral gavage of JM216 as part of the schedule dependency antitumor experiments described above [20], At doses of 9.5,40 (day 1), 40 (day 5) and 200 mg/kg, non-linear pharmacokinetics were observed, both in terms of total and ultrafilterable platinum. On comparing doses of 9.5 and 40 mg/kg, the AUCs increased by tenfold and out of proportion to the fourfold increase in dose. Conversely, a further fivefold increase in dose to 200 mg/kg (the maximum tolerated for single-dose administration) was accompanied by only a twofold increase in AUC, consistent with saturable absorption. Similar Cmax and AUC values for total and ultra-filterable platinum were obtained on day 5 vs. day 1 for the 40 mg/kg dose level. [Pg.507]

Another method, useful In some applications. Is measurement of serum or urinary levels of a given substance following oral administration of pharmacologic doses of test substance. These techniques are similar In concept to tolerance tests such as those for glucose, folic acid or vitamin B-12 and like those may provide clues for determination of absorptive abnormalities. These techniques do not, however, provide a means to assess absorption since they Involve so many uncontrolled variables. For zinc, several such studies have recently been conducted (15-20). [Pg.69]

An oral ADME (absorption, distribution, metabolism, excretion, following oral administration of the pesticide) study may also be of utility in refining the risk assessment. If a default value for dermal absorption of 100 % is applicable based on the physico-chemical properties of a substance and an appropriate oral ADME study is available, the results of this study may be used to refine the default value for dermal absorption. It is required that the oral absorption is determined at low dose levels in experimental animals, in order to obtain an accurate estimate of the oral absorption. Based on theoretical grounds and supported by a comparison of oral and dermal absorption data available for twelve pesticides, it is assumed that dermal absorption will not exceed oral absorption (Hakkert et al unpublished data). [Pg.332]

Utilizing the RIA procedure for serum and urine and in vitro isotope dilution procedure for feces, the absorption and elimination profile of lisinopril was determined in 12 healthy male volunteers following oral administration of a 10 mg capsule (2). The obsenred peak serum concentration was 95 + 55 nM with a time to peak of 7 + 1 hours and an AUC (0-72 hours) of 1694 + 808 nmol liter" hr. The serum concentration vs. time profile was polyphasic and the terminal half-life was approximately 30 hours. The renal clearance was 106 + 13 ml/min with urinary and fecal recovery of 29% + 15% and 69% + 23%, respectively, indicating the drug was excreted unchanged. [Pg.272]

The release rate of methotrexate encapsulated in the internal phase of W/OAV emulsions, stabilized by an interfadal interaction between albumin and sorbitan monooleate, was measured as function of two formulation variables— the oil phase and the secondary emulsifier composition. The release rate was significantly affected by the nature of the oil phase and surfactants with high HLB values (Omotosho et al., 1989). The influence of the oil phase of the W/ OAV emulsions on the oral absorption of 5-fluorouracil in the rat was determined by measuring liver and lymphatic accumulations of the drug. The multiple emulsion system showed potential as a lymphotropic carrier to the mesenteric lymph nodes following oral administration (Omotosho et al., 1990). [Pg.237]

Absorption, Distribution, Metabolism, and Excretion. There are no data available on the absorption, distribution, metabolism, or excretion of diisopropyl methylphosphonate in humans. Limited animal data suggest that diisopropyl methylphosphonate is absorbed following oral and dermal exposure. Fat tissues do not appear to concentrate diisopropyl methylphosphonate or its metabolites to any significant extent. Nearly complete metabolism of diisopropyl methylphosphonate can be inferred based on the identification and quantification of its urinary metabolites however, at high doses the metabolism of diisopropyl methylphosphonate appears to be saturated. Animal studies have indicated that the urine is the principal excretory route for removal of diisopropyl methylphosphonate after oral and dermal administration. Because in most of the animal toxicity studies administration of diisopropyl methylphosphonate is in food, a pharmacokinetic study with the compound in food would be especially useful. It could help determine if the metabolism of diisopropyl methylphosphonate becomes saturated when given in the diet and if the levels of saturation are similar to those that result in significant adverse effects. [Pg.108]

This expression, which relies on fairly rapid absorption such that each subsequent dose is administered in the post-absorptive phase, can be readily employed to determine the extent of accumulation following extravascular administration of a drug as long as dosing interval and the elimination rate constant of the drug are available. Note the similarity between Eq. 12.27 for multiple oral dosing and Eqs 11.29,11.33 and 11.34 for multiple intravenous bolus administration. [Pg.250]

The intravenous administration of a second isotopic label can also be used to assess true absorption of the oral isotopic labels for elements that are excreted via the kidneys, such as calcium and magnesium. As in plasma appearance studies, the intravenous label serves as a reference dose. When the second label is infused or injected slowly following administration of the labeled test meal, both labels appear in parallel in serum/plasma. Some of the circulating labels, however, are excreted via the kidneys, during which the amount ratio of the two labels in blood should ideally be preserved. If this is so, a single spot urine sample can be used, at least in theory, to determine the amount ratio of the two labels in serum. As the intravenous dose is known, this ratio can then be converted into the amount of oral label absorbed. As for most stable isotope techniques, this method was originally developed for radiotracers [31] and adapted for stable isotopes in the 1980s [32]. [Pg.447]


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See also in sourсe #XX -- [ Pg.172 ]




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