Urine pharmacokinetic data

Our pharmacokinetic data indicate that detectable PCP levels may remain in the urine for 4 to 5 weeks after the last use, similar to previous reports (Khajawall and Simpson 1983). The observed elimination kinetics were equally consistent with a one- or two-compartment model, but methodological problems with our data make... 

It has been stated that the dark urine is a result of oxidation products of phenol (Baker et al. 1978). The dark urine may also be a result of increased hemoglobin in the urine as suggested by the Merliss (1972) case report. In this case it took 2-3 months for the urine to clear after exposure was ended, which is not consistent with pharmacokinetic data that indicate that absorbed phenol is excreted in the urine in 1 day (Piotrowski 1971). A study in rats treated dermally with phenol, which found severe hemoglobinuria and hematin casts in the tubules (Conning and Hayes 1970), suggests that hemoglobin or hemoglobin breakdown products could contribute to the dark urine observed in humans. 

Pharmacokinetics Human pharmacokinetics data are limited. Based on preclinical data, it is slowly absorbed into systemic circulation from the eye after intravitreous administration. Metabolized by endo- and exonucleases. Excreted in urine. Half-life 10 days (plasma). 

A plasma calibration curve for ll-nor-A9-THC-9-carboxylic acid, 5a, is shown in Figure 9. There was reasonable linearity from 1.0-50 ng/ml plasma with detection limits of 0.5 ng or less per ml. Figure 10 presents similar data for a urine calibration curve. The method showed reasonable linearity between 2.0-100 ng/ ml urine. Figure 11 presents pharmacokinetic data. for plasma levels of a human volunteer, BS, over a 0.5 hour to 48 hour period comparing A9-THC and 11-nor acid levels after a dose of 5.0 mg of A9-THC by the intravenous route. Both parent compound and acid metabolite exhibited a biphasic elimination pattern although the levels of the acid did not fall as rapidly as parent compound. Elimination of the acid metabolite 5a in urine is shown in Figure 12. It is evident that urinary elimination proceeded rapidly as 80% of the total 11-nor-acid excreted was eliminated in the urine during... 

We present for the first time pharmacokinetic data in plasma and urine obtained by GLC-MS for the important acid metabolite 11-nor-A9-THC-9-carboxylic acid. This and related acids constitute the major means by which A9-THC is excreted in the urine. The data indicate rapid elimination of the acid in the urine during the first 3-6 hours after administration of A9-THC. 

Urinary b-p-hydroxy-cortisol and free cortisol The following pharmacokinetic variables were derived from urine concentration data for 6-P-hydroxy-cortisol and free cortisol on Days 1 and 10 using SAS for Windows protocols amount excreted during each collection interval for 6- 3-hydroxy-cortisol and free... 

Reconstructive exposure assessment uses biological monitoring data, in conjunction with pharmacokinetic data and models, to estimate the levels of absorbed dose (e.g., systemic levels in plasma or whole blood), and in some cases, external exposure to a chemical that resulted in the measured levels in biological tissues and/or fluids. Biological monitoring consists of the measurement of the concentration of a chemical and/or its biotransformation products in biological tissues or fluids (e.g., adipose tissue, blood, urine) or the measurement of the amount of chemical bound to a target molecule (e.g., DNA-bound chemical). 

Of particular importance is the collection of pharmacokinetic data showing the relationship between low-level exposure (acute, intermediate, and chronic) and blood and urine levels throughout the study. duration. Also tissue levels at necropsy should be taken immediately after cessation of dosing. In animal studies, a similar group of animals should be followed for urine (and blood, but not as important here) mercury levels for periods of 30, 60, 90, and 120 days postdosing to examine whole-body excretion, and necropsy tissue samples should also be taken from several animals at 30, 60, 90, and 120 days postdosing. Primates would be the best animal model, but rodent models could suffice. 

An alternative method of getting pharmacokinetic data is to take a small extra sample of blood (and urine) at a child s regular scheduled visit when blood is drawn for routine blood work. The time of day of this sample is predetermined by the time of the administration of the medicine. If samples are obtained from many children, a weight-age-cor-rected, scatter-plot graph can be constructed and a pharmacokinetic profile be calculated. This is the pharmacokinetic screen method. A version of this method is also utilized to gather ethnic data for labeling in adults as well as children, and is called population pharmacokinetics . 

Approximately one hundred studies have been published to date on the bioavailability and pharmacokinetics of individual polyphenols following a single dose of pure compound, plant extract or whole food/beverage to healthy volunteers. We recently reviewed the pharmacokinetic data available for each class to estimate average pharmacokinetic parameters including the maximum concentration in plasma (Qnax)> Tmax> the area under the plasma concentration versus time curve (Al/Q, ehmination half-life (Ti/2) and percent of dose excreted in urine (Manach and Donovan 2004). Here, we present a summary of that data... 

No data were located concerning whether pharmacokinetics of endosulfan in children are different from adults. There are no adequate data to determine whether endosulfan or its metabolites can cross the placenta. Studies in animals addressing these issues would provide valuable information. Although endosulfan has been detected in human milk (Lutter et al. 1998), studies in animals showed very little accumulation of endosulfan residues in breast milk (Gorbach et al. 1968 Indraningsih et al. 1993), which is consistent with the rapid elimination of endosulfan from tissues and subsequent excretion via feces and urine. There are no PBPK models for endosulfan in either adults or children. There is no information to evaluate whether absorption, distribution, metabolism, or excretion of endosulfan in children is different than in adults. 

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. 

The RCR can be determined from urine and plasma data using Eq. (18), and the TCR can be determined from the pharmacokinetic parameters using Eq. (19). Alternately, the RCR can be calculated by multiplying the TCR by the fraction of the dose excreted unchanged into urine,/), ... 

The required data generally are obtained by administering a measured dose of the candidate compound -- often isotopically labelled -- to the rat or mouse either by injection or per os. The animal is housed in a glass metabolism "cage" where it receives food, water, and clean air, and its urine, feces, and respired gases are collected and examined for the parent chemical and its metabolites. Eventual postmortem tissue analysis and calculation of material balance complete the measurements necessary to satisfy the above purposes of metabolism and pharmacokinetic experiments. While in vitro biochemical studies are important adjuncts, it is also apparent that only experiments with intact, healthy, living animals will suffice to meet EPA criteria. 

The closely related herbicides have some differences in distribution and pharmacokinetics which are largely resolved by returning to the observation above that the water solubility of 2,4-D is about 3-fold greater than that of 2,4,5-T. Thus, 2,4-D has initial and final t., values as well as clearance value, about 3 times those founa for 2,4,5-T. These data all fit with the major distribution difference of these 2 compounds, i.e., that considerably more of the dose of 2,4-D is excreted in the urine in 24 hrs. 

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