Urine children, metabolites

Thus, a multiple dose study was performed in which all healthy and hepatic impaired individuals, received the same dose. It was the aim to include 12 patients with various and well distributed degrees of hepatic impairment (according to the Child-Pugh score) and 12 pair-matched (based on demographic characteristics) healthy subjects, in order to have 10 patients and 10 subjects evaluable. The pharmacokinetics of XYZ123 in plasma (total and unbound) and in urine was assessed after the first dose and at steady state after the seventh dose. The pharmacokinetics in plasma of its main metabolite XYZ456 was also assessed. 

A neonatal withdrawal syndrome has been described, with verification by the detection of pentazocine and its metabolites in the urine of both mother and baby. Within 4 hours of birth the child was irritable, jittery, and hypertonic, with a high-pitched cry, a voracious appetite, and frequent bowel movements. The symptoms improved over 3 days. The mother had abused parenteral pentazocine (23-46 mg) for the previous 10 years and injected the last dose of 46 mg some 10 hours before dehvery (10). 

In the first case of citrullinemia reported (M6), intermediary metabolites of the pyrimidine pathway were not sought in the urine. In the second, orotic acid was tested for, but not detected (M12). In the third child, orotic acid, uridine, and uracil were found in relatively large amounts in the urine when the plasma glutamine was at the very high level of 41.0 mg/100 ml, showing that in this genetic disorder, as in the other disorders of urea synthesis, these metabolites are always excreted in excess when the glutamine is raised (VI). 

RDX has been detected in the serum, urine, and feces of one child who consumed unknown levels of RDX in the form of C-4 (91 % RDX). RDX was measured in the serum for 120 hours and in the feces for 144 hours after the presumed time of ingestion (Woody et al. 1986). The metabolities of RDX have only been found in animals by using a radiolabel ( C) (Schneider et al. 1977). Although this study found the radiolabel in the breath, urine, and feces, the chemical identity of the metabolites was not described. Therefore, metabolites cannot currently be used as biomarkers. In the one available human case study, RDX was found in the body following a single exposure, but no data are available regarding intermediate or chronic exposures. 

Biomarkers of Exposure and Effect. Urine or blood levels of RDX are the only known biomarkers of exposure for RDX. These biomarkers have only been demonstrated in a single case report of a child exposed one time (Woody et al. 1986). Therefore, the exposure level cannot be correlated to the levels in the body fluids for other people. Metabolites of RDX cannot be detected unless they are radiolabeled (Schneider et al. 1977). Further studies on determining the correlation between exposure and RDX levels in blood or urine would be useful in developing these levels as biomarkers. 

Hydroxylation. Urinary acids hydroxylated at position 6, especially 6a, include hyodeoxycholate, hyocholate, 3a,6 /, 12a-trihydroxy- and 3a,6a,7a,12 -tetrahy-droxy-5 -cholanates. Hyocholate, the major bile acid in urine, serum and duodenal fluid of a child with intrahepatic cholestasis [109], is a major urinary metabolite of chenodeoxycholate in patients with intrahepatic cholestasis, while 3a,6a,12a-trihy-droxy-5j3-cholanate is only a minor metabolite of deoxycholate [123]. The 3a,6a,7a,12a-tetrahydroxy acid, obtained from urine of patients with liver diseases [194] and from gastric contents of neonates with duodenal atresia [203] is another metabolite of cholic acid [123] several unidentified tetrols have yet to be char-... 

Evidence that purine metabolism is important in the immune response has been obtained from the observation that markedly reduced or absent adenosine deaminase (ADA) activity in man has been casually associated with an autosomal recessive form of severe combined immunodeficiency disease (3). Recently, ADA levels in lymphocytes from patients with untreated chronic lymphatic leukemia have been found to be consistently lower than in lymphocytes from normal subjects (4). Children with ADA deficiency and immunodeficiency have been shown to have increased levels in plasma, urine, lymphocytes and erythrocytes of adenosine, adenine, deoxy-adenosine, adenine nucleotides, and deoxyadenine (5, 6). Although the exact biochemical mechanism(s) is unknown, elevated levels of adenosine, and/or deoxyadenosine and their metabolites are thought to be selective inhibitors of both differentiation and effector function of lymphocytes (7, 8). Adenosine was known to inhibit the PHA-induced blastogenesis of human peripheral blood lymphocytes (9) even before the discovery of the first ADA-deficient child. In addition, elevated levels of cyclic AMP (cAMP) were known to be inhibitory for lymphocyte-mediated cytotoxicity (7). Since... 

Fig. 7.2 Chromatogram of acidic metabolites extracted from the urine of a normal child using DEAE-Sephadex and re-extraction with solvents after ethoxime formation and freeze-drying by reconstitution in water, acidification with hydrochloric acid, saturation with sodium chloride, and solvent extraction with diethyl ether (three times) and ethyl acetate (three times), evaporation of the solvents from the combined extracts using dry nitrogen and trimethylsilylation using the minimum quantity of BSTFA. Separated on 10 per cent OV-101 on HP Chromosorb W (80-100 mesh) by temperature programming from 110°C to 285°C at 4°C min with an initial 5 min isothermal delay. Peak identifications are 1, phenol plus lactate 2, glycollate 3, cresol 4, 3-hydroxyisovalerate 5, benzoate 6, phosphate 7, succinate 8, 3-methyladipate 9, 3-hydroxy-3-methyl-glutarate 10, 4-hydroxyphenylacetate 11, homovanillate plus some aconitate 12, hippurate 13, citrate 14, vanilmandelate 15, n-tetracosane (standard) 16, n-hexacosane (standard).

Fig. 7.5 Chromatogram of acidic metabolites extracted from the urine of a 1.5-year-old child using DEAE-Sephadex and separated as described in the legend to Fig. 7.3. Peak identification numbers correspond to those used in Fig. 7.4. Peak 25a is a-glycero-pliosphate. (Compare to Fig. 7.1)...

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