Urinary excretion studies

The earliest reports of controlled release steroids were those of Jackanicz (63), Yolles (64), Anderson (65), and Wise (66). Most of those early studies were based on poly[ (L+)-lactic acid). Implants and granular particles were fabricated with progesterone, norgestrel, and norethisterone. In vivo urinary excretion studies were conducted on [I Cjprogesterone beads (64). The reported results were somewhat questionable as only 20% of the original implanted drug could be accounted for. 

Example. The plot in Fig. 6 was constructed using the data shown in Table 3. Note that the concentration of the drug in each urine specimen is not the information analyzed. The total amount excreted over each time interval and throughout the entire study must be determined. As a result, the experimental details of a urinary excretion study must be very carefully chosen, and strict adherence to the protocol is required. Loss of a single urine specimen, or even an unknown part of a urine specimen, makes construction of an ARE plot impossible. 

It should be noted that for urinary excretion studies the preferred design is to collect 24 h urine. In some special designs it can be argued that the use of spot urine samples and correction for urinary creatinine concentration may be a valid measure. A prerequisite for the spot urine - creatinine correction design is a solid argumentation that creatinine excretion is unchanged by the experimental condition or that it is not different between groups. A theoretical example is comparison of lean men versus fat females. Their cell number is comparable but muscle mass very different. Creatinine excretion is mainly... 

W. A. Ritschel and M. Banarer. Correlation between in vitro release of proxyphyUine from suppositories and in vivo data obtained from cumulative urinary excretion studies. Arzneim Forsch., 23, 1031-5 (1973)... 

Swenseid, M. A., Bird, O. D., Brown, R. A., and Bethell, F. H., Metabolic function of pteroylglutamic acid and its hexaglutamate conjugase. II. Urinary excretion studies on normal persons. Effect of a conjugase inhibitor. J. Lab. Clin. Med. 32, 23-27 (1947). 

In animal cells, 4-HB is formed from the essential amino acid tyrosine. A pathway for the conversion of tyrosine to 4-HB was proposed by Booth et following urinary excretion studies on animals administered with various phenolic acids. Based on these studies and the incorporation of radiolabeled phenolic acids into Q by... 

Human exposure to environmental contaminants has been investigated through the analysis of adipose tissue, breast milk, blood and the monitoring of faecal and urinary excretion levels. However, while levels of persistent contaminants in human milk, for example, are extensively monitored, very little is known about foetal exposure to xenobiotics because the concentrations of persistent compounds in blood and trans-placental transmission are less well studied. Also, more information is needed in general about the behaviour of endocrine disruptive compounds (and their metabolites) in vivo, for example the way they bind to blood plasma proteins. 

Nitrophenol and 4-nitrophenol glucuronide are excreted in urine. The studies of urinary excretion of methyl parathion metabolites, including those reported in this section, generally hydrolyze the glucuronide prior to analysis and report the resulting total 4-nitrophenol values. 

The study of the mechanism of urinary excretion of amylase and the amylase clearance has been the subject of many studies in recent years. Levitt et. al (79) studied the renal clearance of amylase in renal insufficiency, acute pancreatitis and macro-amylasemia. In acute pancreatitis, the kidney cleared amylase at a markedly increased rate. The ratio of the amylase clearance rate to the creatinine clearance rate (Cgm/Ccr) averaged 3 times normal early in the course of acute pancreatitis, and this elevation could persist after the serum amylase returned to normal. Comparison of an lase clearance to creatinine clearance was to minimize irrelevant changes due to variation in renal function. The increased clearance of amylase makes the urinary amylase a more sensitive indicator of pancreatitis. 

The primary urinary metabolites of trichloroethylene in humans are trichloroethanol, trichloroethanol glucuronide, and TCA (Monster et al. 1979 Nomiyama and Nomiyama 1971 Sato et al. 1977). The halftime for renal elimination of trichloroethanol and trichloroethanol glucuronide has been determined in several studies to be approximately 10 hours following trichloroethylene exposure (Monster et al. 1979 Sato et al. 1977). The urinary excretion of TCA is much slower, and data from several studies indicate that the halftime of urinary TCA is approximately 52 hours because the metabolite is very tightly and extensively bound to plasma proteins (Monster et al. 1976 Sato et al. 1977). 

Morabito et al., 2002 European postmenopause placebo, n = 30 genistein, n = 30 HRT, n = 30 First randomized, double-blind placebo-controlled study. Compared to placebo control, genistein (54 mg/day) consumed for 1 year significantly reduced urinary excretion of bone resorption markers and increased bone formation markers at 6 and 12 months BMD was significantly increased at the femoral neck and lumbar spine plasma genistein concentration was around 1.5 pM. HRT showed similar effects to genistein for BMD. 

No studies were located regarding toxicokinetic data in humans. Limited information is available regarding the toxicokinetic differences among animal species. Rats, mice, mink, and dogs showed rapid absorption, wide distribution, and over 90% urinary excretion of diisopropyl methylphosphonate or its metabolites. However, the rates of absorption and patterns of distribution varied (Hart 1976 Weiss et al. 1994). The mechanism of toxicity is also undetermined. From the limited data available, it is not possible to determine the degree of correlation between humans and animals. 

Exposure. Few studies were found regarding the measurement of diisopropyl methylphosphonate or its metabolites as indicators of exposure. IMPA in urine or plasma has been suggested as a biomarker of acute exposure. It would be useful to more fully explore urinary excretion of IMPA to determine dose relationships and its utility as a bioindicator of diisopropyl methylphosphonate exposure. 

Studies with rats treated orally with triaryl or trialkyl phosphate esters (which may be found in organophosphate ester hydraulic fluids) indicate that these compounds and their metabolites are readily excreted in the urine, bile, feces and, to a limited extent, in expired air (Kurebayashi et al. 1985 Somkuti and Abou-Donia 1990a Suzuki et al. 1984a Yang et al. 1990). Urinary excretion of metabolites appears to be the predominant elimination route in rats for tri-ort/zo-cresyl phosphate and tri-para-cresyl phosphate, but biliary excretion of parent material and metabolites is also important (Kurebayashi et al. 1985 NTP... 

As indicated, the ionized form of a drug will be more soluble than the nonionized form in the aqueous fluids of the GIT. The classic studies on the beneficial effects of changing nonionized drugs into salt forms were reported by Nelson for tetracycline [25], and Nelson et al. for tolbutamide [26]. Table 2 combines portions of the data from each study. Urinary excretion of the drug or its metabolite was taken as the in vivo measure of the relative absorption rate for the salt and the nonionized... 

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