elimination constant
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2017 ◽  
Vol 15 (1) ◽  
pp. 48-52
Author(s):  
Rodion A Oseshnyk ◽  
Inna E Ushal ◽  
Ekaterina V Svetkina ◽  
Ekaterina A Kolobova ◽  
Yury V Strukov ◽  
...  

The data of inter-individual variations in pharmacokinetics of antiblastomic drugs from the group of tyrosine proteinkinase inhibitors (imatinib, gefitinib and nilotinib) and antiblastomic immune modulator lenalidomide in healthy volunteers by meams of HPLC-MS/MS were represented in the article. The concentrations of the drugs studied were measured in the volunteer blood serum. The indeces Cmax (maximal concentration and time reaching), Tmax (time covering maximal concentration measure), AUC0-t (squire under pharmaceutical curve) were processed by trapetias method, Cmax/AUC0-t as well as Kel (elimination constant) and T1/2 (period of semielimination) according to individual signs. The significant individual variability revealed for imatinib, gefitinib and nilotinib in healthy volunteers indicates on necessity of therapeutic drug monitoring in patients treated with them to aim optimal dosing.


1997 ◽  
Vol 7 (5) ◽  
pp. 515-540 ◽  
Author(s):  
ANDREW W. APPEL ◽  
TREVOR JIM

Functional-language compilers often perform optimizations based on beta and delta reduction. To avoid speculative optimizations that can blow up the code size, we might wish to use only shrinking reduction rules guaranteed to make the program smaller: these include dead-variable elimination, constant folding, and a restricted beta rule that inlines only functions that are called just once. The restricted beta rule leads to a shrinking rewrite system that has not previously been studied. We show some efficient normalization algorithms that are immediately useful in optimizing compilers; and we give a confluence proof for our system, showing that the choice of normalization algorithm does not affect final code quality.


1997 ◽  
Vol 273 (2) ◽  
pp. G355-G364 ◽  
Author(s):  
T. Yamada ◽  
M. Hoshino ◽  
T. Hayakawa ◽  
H. Ohhara ◽  
H. Yamada ◽  
...  

We investigated the effects of dietary diosgenin (Dio), a plant-derived sapogenin, on indomethacin (Indo)-induced intestinal inflammation and alterations in bile secretion in rats. In anesthetized rats, bile secretion, intestinal inflammation, and blood chemistry were assessed 3 days after two subcutaneous injections of Indo given 24 h apart. Dio (> 80 mg.kg-1.day-1) pretreatment significantly inhibited weight and food intake decreases and intestinal inflammation. This protective effect was confirmed by examination of gross and histological findings and intestinal myeloperoxidase activity. Dio significantly increased biliary cholesterol (Chol) output and prevented the decreases in bile flow, bile acid output, and biliary alpha-muricholic acid and the increases in biliary hyodeoxycholic acid, deoxycholic acid, and hydrophobicity index of bile. Significantly more biliary Chol and phospholipids were present in macromolecules separate from bile acids and Indo in Dio-treated rats. Dio significantly increased the elimination constant of Indo and reduced plasma Indo levels at 3 and 12 h but did not influence biliary secretion of Indo for 3.5 h after injection. Although Dio dose-dependently attenuated subacute intestinal inflammation and normalized bile secretion in this model, it may also compromise the anti-inflammatory action of indo.


1986 ◽  
Vol 4 (5) ◽  
pp. 753-761 ◽  
Author(s):  
S L Kelley ◽  
W P Peters ◽  
J Andersen ◽  
E A Furlong ◽  
E Frei ◽  
...  

A combined clinical and pharmacokinetic phase I study of the substituted hexitol dibromodulcitol (DBD), administered as a single oral monthly dose, has been performed. Twenty-three patients with advanced neoplasms received DBD doses ranging from 600 to 1,800 mg/m2 body surface area (BSA). The dose-limiting toxicity was myelosuppression, with both significant granulocytopenia and thrombocytopenia occurring at dose levels of 1,500 to 1,800 mg/m2. The average pharmacokinetic parameters for DBD, calculated on the basis of a one-compartment model with first-order absorption and elimination, include the elimination constant, .005 +/- .002/min; absorption constant, .012 +/- .009/min; and an apparent volume of distribution, 1.03 +/- .4 L/kg. The area under the drug concentration curve (AUC) and the peak drug level (Cmax) were linearly related to the dose administered (P less than .001). The mean AUC was 18.7 +/- 6.1 mmol/L min, and the mean Cmax was 47.1 +/- 16.8 mumol/L when normalized to a DBD dose of 1 gm/m2. The elimination constant was significantly reduced in patients with abnormal hepatic function (P less than .01). The elimination constant was not correlated with renal function. The half-life of DBD in plasma (158 minutes) was considerably shorter than the four-to eight-hour half-life of total radioactivity in plasma measured by previous investigators following the administration of radiolabeled DBD.


1983 ◽  
Vol 17 (12) ◽  
pp. 901-903 ◽  
Author(s):  
Rosalie Sagraves ◽  
J. Chris Bradberry

A 26-month-old child was admitted to the pediatric intensive care unit for treatment of apparent fulminant hepatitis. While hospitalized, he underwent eight exchange transfusions to decrease ammonia concentrations. The patient received intravenous phenobarbital (Pb) for the treatment of cerebral edema. To determine the effects of exchange transfusion on Pb clearance, serum Pb concentrations were obtained before, after, and between exchanges. Preexchange and postexchange serum Pb concentrations were obtained on three separate exchanges. Pb concentrations also were examined between two exchange transfusions. The amount of Pb actually removed during one exchange transfusion was determined by analyzing serum obtained from the discarded blood resulting from the procedure. All Pb concentrations were analyzed by the Emit system. Results indicate that Pb was cleared at a mean rate of 433 ml/h during the exchange periods examined, with a mean overall elimination constant of 0.20 h−1. The Pb actually removed by the exchange transfusion on day 10 of hospitalization was determined to be 17 mg, while the calculated amount was 8 mg. A mean of 22.3 mg of Pb was calculated to be removed over an average exchange time of 2.2 hours. Pb clearance during exchange transfusion has not been reported previously. This case has shown that small amounts of Pb can be removed by exchange transfusion; therefore, patients undergoing this procedure may require serum monitoring after exchange.


1980 ◽  
Vol 45 (11) ◽  
pp. 3045-3050 ◽  
Author(s):  
Tomislav Barth ◽  
Jiřina Slaninová ◽  
Michal Lebl ◽  
Karel Jošt

The biological potency and the duration of the effect of two analogues of deamino-oxytocin, having the disulfide bond substituted by a thioether group and the tyrosine residue replaced by O-methyltyrosine, were compared in the uterotonic and galactogogic assay in vivo. [2-O-Methyltyrosine]deamino-6-carba-oxytocin had a very low formal elimination constant (i.e. strongly protracted action) in the uterotonic assay.


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