scholarly journals Studies on the metabolic fate of 15(R)-15-methylprostaglandin E2 (Arbaprostil) in human. (II) - Plasma concentration and urinary excretion of intact drug and its epimer form.

Author(s):  
Hisayuki SEKINO ◽  
Noboru NAKAMICHI ◽  
Kazuhiro NISHIMIYA ◽  
Yasutsugu OHSAWA ◽  
Akira OKAZAKI
1991 ◽  
Vol 39 (4) ◽  
pp. 1068-1071
Author(s):  
Nobuo KAWABATA ◽  
Kenichi YANO ◽  
Hiromitsu OHNO ◽  
Toshiaki NAKASHIMA

1982 ◽  
Vol 33 (5) ◽  
pp. 843 ◽  
Author(s):  
IR Godwin ◽  
VJ Williams

The effects of calcium, phosphorus and magnesium contents of diets containing different proportions of wheat grain to roughage on the excretion of minerals involved in urinary calculi formation by sheep, were examined in three separate studies: the first, with six sheep, determined the effects of increasing the percentage of wheat grain in the diet on the digestibilities of Ca, P and Mg, the excretion of these three elements in urine and on the propensity of the diets to form calculi; the second involved two sheep and studied the effects of supplementing a 90% grain diet with CaCO3 and roughage on faecal and urinary excretion of Ca, P and Mg; the third was carried out using four sheep fed on a 75 % grain diet and examined the effects of supplementation with extra P, Ca and roughage on Ca, P and Mg excretion. Urinary P concentration was directly correlated with the formation of calculi. Plasma inorganic phosphorus (P,) increased when grain in the diet was 75 % or greater and this led to increased urinary P excretion. The addition of CaCO3 reduced urinary P without large changes in plasma P1 and increased the faecal output of P. Extra roughage added to high grain diets reduced the digestibility of both Ca and P and the plasma concentration and urinary excretion of P. The significance of these findings for the prevention of urinary calculi in sheep is discussed.


2000 ◽  
Vol 10 (2) ◽  
pp. 127-135 ◽  
Author(s):  
Yusuke Arai ◽  
Mariko Uehara ◽  
Yuho Sato ◽  
Mitsuru Kimira ◽  
Akira Eboshida ◽  
...  

PEDIATRICS ◽  
1969 ◽  
Vol 44 (2) ◽  
pp. 201-208
Author(s):  
S. Douglas Frasier ◽  
Richard Horton ◽  
Robert A. Ulstrom

The plasma concentration of androstenedione and testosterone, metabolic clearance rate of androstenedione, and in vivo conversion ratio of androstenedione to testosterone have been studied in a normotensive 5-year-old female with congenital adrenal hyperplasia due to a deficiency of 11 β-hydroxylase. Prior to glucocorticoid administration, the urinary excretion of 17-ketosteroids varied from 2.2 to 4.9 mg/24 hours, urinary excretion of pregnanetriol varied from 0.7 to 2.2 mg/24 hours, and total 17-hydroxysteroid excretion varied from 1.2 to 7.5 mg/24 hours. Urinary tetrahydro-11-deoxy cortisol (TSH) was detected at a concentration of 550 µg/24 hours. The plasma concentration of androstenedione varied from 100 to 530 mµg/100 ml and the plasma concentration of testosterone varied from 40 to 90 mµg/100 ml. These values are significantly elevated when compared to those obtained in normal prepubertal females. Urinary steroid excretion and plasma androgen concentrations fell to normal in response to glucocorticoid administration. The metabolic clearance rate of androstenedione was 890 liters per day per M2 and the in vivo conversion ratio of androstenedione to testosterone was 11%. The calculated production rate of androstenedione was 4.7 mg per day per M2. Virilization in congenital adrenal hyperplasia due to 11 β-hydroxylase deficiency can be explained by an elevated plasma concentration of testosterone, which can be accounted for on the basis of conversion from androstenedione.


1988 ◽  
Vol 6 (3) ◽  
pp. 517-526 ◽  
Author(s):  
K Mross ◽  
P Maessen ◽  
W J van der Vijgh ◽  
H Gall ◽  
E Boven ◽  
...  

Pharmacokinetics of doxorubicin (DOX), epidoxorubicin (EPI), and their metabolites in plasma have been performed in eight patients receiving 40 to 56 mg/m2 of both anthracyclines as a bolus injection in two sequential cycles. Terminal half-life and volume of distribution appeared to be smaller in case of EPI, whereas plasma clearance and cumulative urinary excretion was larger in comparison to DOX. The major metabolite of DOX was doxorubicinol (Aol) followed by 7-deoxy-doxorubicinol (7d-Aolon). Metabolism to glucuronides was found in case of EPI only. The area under the curves (AUC) of the metabolites of EPI decreased in the order of the glucoronides E-glu greater than Eol-glu, 7d-Aolon greater than epirubicinol (Eol). The AUC of Eol was half of the value in its counterpart Aol. In the case of EPI, the AUC of 7d-Aolon was twice the level of that of the corresponding metabolite of DOX. The terminal half-lives of the cytostatic metabolites Aol and Eol were similar, but longer than the corresponding values of their parent drugs. Half-lives of the glucuronides (E-glu, Eol-glu) were similar to the half-life of their parent drug. 7d-Aolon had a somewhat shorter half-life in comparison to both DOX and EPI. Approximately 6.2% of EPI and 5.9% of DOX were excreted by the kidney during the initial 48 hours. Aol was found in the urine of patients treated with DOX, whereas Eol, E-glu, and Eol-glu were detected in urine of patients treated with EPI. The cumulative urinary excretion appeared to be 10.5% for EPI and its metabolites, and 6.9% for DOX and its metabolite. The plasma concentration v time curves of (7d)-aglycones showed a second peak between two and 12 hours after injection, suggesting an enterohepatic circulation for metabolites lacking the daunosamine sugar moiety. The plasma concentrations of the glucuronides were maximal at 1.2 hours for E-glu and 1.9 hours for Eol-glu. All other compounds reached their maximum plasma concentration during the first minutes after the administration of DOX and EPI. Deviating plasma kinetics were observed in one patient, probably due to prior drug administration.


2013 ◽  
Vol 304 (12) ◽  
pp. E1359-E1364 ◽  
Author(s):  
Christina Kao ◽  
Jean Hsu ◽  
Venkata Bandi ◽  
Farook Jahoor

In enterocytes, glutamine serves as the major source of energy; another metabolic fate of glutamine is conversion to citrulline. Because sepsis can affect gut function and integrity, alterations in glutamine metabolism may exist and lead to decreased citrulline production. This study aimed to investigate how sepsis affects glutamine metabolism, including its conversion to citrulline, by measuring glutamine and citrulline flux, fractional splanchnic extraction of glutamine and leucine, and the contribution of glutamine nitrogen to citrulline in septic patients and healthy controls. Eight patients with severe sepsis and 10 healthy controls were given primed, constant intravenous infusion of [2H2]citrulline and sequential administration of intravenous and enteral [α-15N]glutamine and [13C]leucine in the postabsorptive state. The results showed that, compared with healthy controls, septic patients had a significantly lower whole body citrulline flux and plasma concentration, higher endogenous leucine flux, and higher glutamine clearance. Fractional splanchnic extraction of leucine was higher in septic patients than in controls, but fractional extraction of glutamine was not different. The majority of the 15N label transferred from glutamine to citrulline was found at the α-position. These results demonstrate that lower glutamine plasma concentrations in sepsis were a result of increased glutamine clearance. Despite adequate splanchnic uptake of glutamine, there is decreased production of citrulline, suggesting a defect in the metabolic conversion of glutamine to citrulline, decreased uptake of glutamine by the enterocyte but increased uptake by the liver, and/or shunting of glutamine to other metabolic pathways.


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