scholarly journals Plasma concentrations of alpha-1-acid glycoprotein in preterm and term newborns: influence of mode of delivery and implications for plasma protein binding of local anaesthetics

2018 ◽  
Vol 121 (2) ◽  
pp. 427-431 ◽  
Author(s):  
M. Anell-Olofsson ◽  
S. Ahmadi ◽  
P.A. Lönnqvist ◽  
S. Eksborg ◽  
H. von Horn ◽  
...  
2000 ◽  
Vol 20 (6) ◽  
pp. 766-771 ◽  
Author(s):  
David W. Johnson ◽  
Troy D. Kay ◽  
David A. Vesey ◽  
Nicole Isbel ◽  
Scott B. Campbell ◽  
...  

Objectives To investigate the degree and the determinants of peritoneal homocysteine (Hcy) clearance and to compare measured Hcy clearance with the Hcy clearance predicted based on molecular weight (MW). Design Cross-sectional observational analysis. Setting Tertiary care institutional dialysis center. Patients Sixty-five stable peritoneal dialysis (PD) patients. Outcome Measures Fasting blood and 24-hour pooled dialysate effluents were collected for determination of peritoneal clearances of Hcy (CpHcy), urea (CpUr), and creatinine (CpCr). The dialysate-to-plasma creatinine ratio at 4 hours (D/P Cr 4 h) and levels of red cell folate, B12, ferritin, and C-reactive protein (CRP) were measured concurrently. Observed CpHcy was compared with predicted clearance, based on Hcy plasma protein binding and the relative molecular weights of Hcy, urea, and creatinine. Results Plasma concentrations of Hcy averaged 24.6 ± 1.1 μmol/L and were elevated above the upper limit of normal in 59 (91%) patients. The mean dialysate concentration of Hcy was 2.9 ± 0.3 μmol/L, equating to a daily peritoneal elimination of 34.6 ± 3.6 μmol. Observed CpHcy was closely approximated by predicted CpHcy (8.7 ± 0.6 L/week/1.73 m2 vs 9.0 ± 0.3 L/week/1.73 m2 respectively, p = 0.55). Patients maintained on automated PD ( n = 5) had a CpHcy similar to that of patients treated with continuous ambulatory peritoneal dialysis (8.9 ± 1.0 L/week/1.73 m2 vs 8.7 ± 0.6 L/week/1.73 m2, p = 0.92). The CpHcy was significantly correlated with C-reactive protein (CRP), D/P creatinine, CpUr, CpCr, and peritoneal protein loss, but not with plasma Hcy, albumin, B12, ferritin, age, dialysis duration, peritonitis episodes, or daily dialysate effluent volume. By multivariate analysis, the only variables that remained significant independent predictors of CpHcy were CRP and D/P Cr 4 h. High and high-average transporters had a higher CpHcy than low and low-average transporters (9.7 ± 0.8 L/week/1.73 m2 vs 7.0 ± 0.7 L/week/1.73 m2, p < 0.05), despite comparably elevated plasma Hcy concentrations [25.2 ± 1.5 μmol/L vs 23.4 ± 1.6 μmol/L, p = nonsignificant (NS)]. Conclusions Elevated plasma concentrations of Hcy are not efficiently reduced by PD. The relatively low peritoneal clearance of Hcy is largely accounted for by a high degree of plasma protein binding and is significantly influenced by peritoneal membrane permeability.


1993 ◽  
Vol 27 (1) ◽  
pp. 32-35 ◽  
Author(s):  
Barry E. Gidal ◽  
D. Michael Collins ◽  
Brad R. Beinlich

OBJECTIVE: To report a case of possible neurotoxicity caused by markedly elevated free valproic acid (VPA) plasma concentrations. CASE SUMMARY: A patient with a history of a mixed-type seizure disorder that had been treated with oral VPA 1000 mg four times daily for the previous two years was admitted to the neurology service with the chief complaint of increasing difficulty in walking and involuntary muscle jerks that were new in onset. The patient was hypersomnolent and dysarthric. The total plasma VPA concentration was 103 μg/mL, which was only slightly above the recommended therapeutic range (50–100 μg/mL). VPA free fraction and free plasma concentrations, however, were unexpectedly elevated (26 percent, 26.8 μg/mL, respectively). Further laboratory evaluation revealed a serum albumin concentration of 33 g/L. The neurologic symptoms resolved upon VPA dosage reduction. DISCUSSION: VPA displays concentration-dependent protein binding, resulting in disproportionate increases in drug free fraction with increasing drug concentration. This effect may be magnified in patients with decreased plasma protein-binding capacity. The plasma protein-binding kinetics of VPA are reviewed and the implications for therapeutic drug monitoring are discussed. CONCLUSIONS: It is likely that the markedly elevated free VPA plasma concentrations contributed to the neurologic symptoms displayed in this patient. In patients with decreased albumin concentrations, failure to recognize concentration-dependent protein binding, as well as exclusive reliance upon total drug concentrations, may lead to erroneous pharmacokinetic and therapeutic interpretations.


2008 ◽  
Vol 16 (7) ◽  
pp. 3759-3772 ◽  
Author(s):  
Ferenc Zsila ◽  
Júlia Visy ◽  
György Mády ◽  
Ilona Fitos

2013 ◽  
Vol 57 (10) ◽  
pp. 5147-5150 ◽  
Author(s):  
Caroline Barau ◽  
Valérie Furlan ◽  
Yazdan Yazdanpanah ◽  
Catherine Fagard ◽  
Jean-Michel Molina ◽  
...  

ABSTRACTThe objective of this study was to characterize raltegravir (RAL) binding to albumin and alpha-1-acid glycoprotein (AAG). Unbound and bound RAL were separated by ultrafiltration. The association constant (Ka) was estimated by a graphical method. In HIV-infected patients, the average plasma protein binding is 76%. RAL did not bind to AAG but bound to nonsaturable, low-affinity albumin sites with ann(number of sites) ·Kaproduct of 9.8 × 102liters/mol. A pH increase of 0.2 U led to a 2% increase in the bound fraction.


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