The kinetics of the auto-induction of ifosfamide metabolism during continuous infusion

1995 ◽  
Vol 36 (1) ◽  
pp. 53-60
Author(s):  
A. V. Boddy ◽  
Michael Cole ◽  
Andrew D. J. Pearson ◽  
Jeffrey R. Idle
1980 ◽  
Vol 238 (5) ◽  
pp. E473-E479 ◽  
Author(s):  
D. E. Matthews ◽  
K. J. Motil ◽  
D. K. Rohrbaugh ◽  
J. F. Burke ◽  
V. R. Young ◽  
...  

Leucine metabolism in vivo can be determined from a primed, continuous infusion of L-[1-13C]leucine by measuring, at isotopic steady state, plasm [-13C]leucine enrichment, expired 13CO2 enrichment, and CO2 production rate. With an appropriate priming dose of L-[1-13C]leucine and NaH13CO3, isotopic steady state is reached in less than 2 h, and the infusion is completed in 4 h. The method can determine rates of leucine turnover, oxidation, and incorporation into protein with typical relative uncertainties of 2, 10, and 4%, respectively. The method requires no more than 1 ml of blood and uses stable isotope rather than radioisotope techniques. Thus, the method is applicable to studies of human beings of all ages. L-[1-13C]leucine may be infused with a second amino acid labeled with 15N for simultaneous determination of the kinetics of two amino acids.


1990 ◽  
Vol 18 (2) ◽  
pp. 292-293 ◽  
Author(s):  
STEPHEN GORE ◽  
ANTHONY I. MORRIS ◽  
IAN T. GILMORE ◽  
DAVID BILLINGTON

1995 ◽  
Vol 36 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Alan V. Boddy ◽  
Michael Cole ◽  
Andrew D. J. Pearson ◽  
Jeffrey R. Idle

1982 ◽  
Vol 47 (2) ◽  
pp. 301-309 ◽  
Author(s):  
R. M. Dixon ◽  
J. V. Nolan ◽  
L. P. Milligan

1. Experiments were undertaken to examine the errors associated with the use of indigestible markers, the 51Cr-labelled complex of chromium ethylenediaminetetra-acetic acid (51Cr-EDTA) and 103Ru-labelled tris-(1,10-phenanthroline)-ruthenium(II) chloride (103Ru-P), to measure liquid- and solid-phase digesta kinetics in the caecum and proximal colon of sheep.2. First-order kinetics of markers were observed following either single injection or termination of continuous infusion. There were no differences between the half-times (T½) of marker in the caecum plus proximal colon whether calculated from marker concentration in caecal digesta or in faeces. There were also no differences in the T½ values calculated for the liquid- and solid-phase markers. When pool sizes calculated from the marker kinetics were compared with the volume of digesta present in the caecum and proximal colon at slaughter, it appeared that the 51Cr-EDTA and 103Ru-P caecal pools described the digesta contained in the entire caecum and proximal colon.3. The flow-rates of dry matter (DM) through the caecum of sheep given 694 g lucerne (Medicago sativa) DM/d were similar whether estimated from total collection of faeces, by single injection of marker, or by the ratio, marker concentration: DM in either caecal digesta or faeces during continuous infusion of marker into either the rumen or the caecum.4. In sheep given 553 g brome grass (Bromus inermus) DM/d the coefficient of variation of estimates of the plateau of 51Cr-EDTA marker during continuous infusion into the caecum was greater when 130 ml infusate/d were administered than with 1000 ml/d.5. In the sheep given brome grass the lines of best fit of decline in In 51Cr-EDTA marker concentration v. time following termination of the continuous infusions described previously and following single injection of marker in 20 or 2 ml into the caecum were examined. The variation was least when 1000 ml infusate/d had been administered and was unacceptably large following a single injection of 2 ml.6. These experiments showed that tracer techniques could provide unbiased estimates of trace kinetics in the caecum and proximal colon.


2010 ◽  
Vol 112 (1) ◽  
pp. 226-238 ◽  
Author(s):  
Albert Dahan ◽  
Leon Aarts ◽  
Terry W. Smith

Opioid treatment of pain is generally safe with 0.5% or less events from respiratory depression. However, fatalities are regularly reported. The only treatment currently available to reverse opioid respiratory depression is by naloxone infusion. The efficacy of naloxone depends on its own pharmacological characteristics and on those (including receptor kinetics) of the opioid that needs reversal. Short elimination of naloxone and biophase equilibration half-lives and rapid receptor kinetics complicates reversal of high-affinity opioids. An opioid with high receptor affinity will require greater naloxone concentrations and/or a continuous infusion before reversal sets in compared with an opioid with lower receptor affinity. The clinical approach to severe opioid-induced respiratory depression is to titrate naloxone to effect and continue treatment by continuous infusion until chances for renarcotization have diminished. New approaches to prevent opioid respiratory depression without affecting analgesia have led to the experimental application of serotinine agonists, ampakines, and the antibiotic minocycline.


1995 ◽  
Vol 268 (1) ◽  
pp. E121-E126 ◽  
Author(s):  
D. Reaich ◽  
K. A. Graham ◽  
S. M. Channon ◽  
C. Hetherington ◽  
C. M. Scrimgeour ◽  
...  

To test the hypothesis that acidosis contributes to the insulin resistance of chronic renal failure (CRF) and impairs the action of insulin to decrease protein degradation, eight CRF patients were studied using the combined L-[1–13C]leucine-euglycemic clamp technique before (acid) and after (NaHCO3) 4 wk treatment with NaHCO3 (pH: acid 7.29 +/- 0.01 vs. NaHCO3 7.36 +/- 0.01, P < 0.001). Protein degradation (PD) was estimated sequentially from the kinetics of a primed continuous infusion of L-[1–13C]leucine in the basal state and during a hyperinsulinemic euglycemic clamp. Insulin sensitivity was measured during the clamp. The correction of acidosis significantly increased the glucose infusion rate necessary to maintain euglycemia (acid 6.44 +/- 0.89 vs. bicarbonate 7.38 +/- 0.90 mg.kg-1.min-1, P < 0.01) and significantly decreased PD in the basal state (acid 126.4 +/- 8.1 vs. bicarbonate 100.1 +/- 6.9 mumol.kg-1.h-1, P < 0.001). Hyperinsulinemia decreased PD in both studies (acid basal 126.4 +/- 8.1 vs. clamp 96.5 +/- 7.7, P < 0.001; bicarbonate basal 100.1 +/- 6.9 vs. clamp 88.2 +/- 5.5 mumol.kg-1.h-1, P = 0.06), its effect being unaltered by acidosis, with a reduction of 24% before and 12% after the correction of acidosis. In conclusion, acidosis contributes to the insulin resistance of CRF but does not affect the action of insulin on PD.


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