Effects of total plasma concentration and age on tolbutamide plasma protein binding

1982 ◽  
Vol 31 (4) ◽  
pp. 488-493 ◽  
Author(s):  
Joseph Adir ◽  
Ann K Miller ◽  
Robert E Vestal
Keyword(s):  
Plasma Concentration ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Total Plasma ◽  
Total Plasma Concentration

Effects of pronounced haemodilution on the plasma protein binding of lidocaine

Perfusion ◽  
1995 ◽  
Vol 10 (1) ◽  
pp. 17-20 ◽  
Author(s):  
PA Lönnqvist ◽  
L. Herngren
Keyword(s):  
Plasma Concentration ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Free Fraction ◽  
Total Plasma ◽  
Free Concentration ◽  
Significant Difference ◽  
Total Plasma Concentration ◽  
Pharmacologically Active

The effects of pronounced haemodilution on the protein binding of lidocaine was investigated in vitro in plasma from five healthy adult volunteers. The plasma was diluted with a phosphate buffer to reach a plasma protein concentration normally seen during paediatric cardiopulmonary bypass (CPB) and protein binding was determined at a low (1.5 μg/ml) and a moderate (4 μg/ml) total plasma concentration of lidocaine. The effects of different haematocrits on plasma protein binding was also determined over the haematocrit range 20-60%. The binding of lidocaine was found to be inversely related to the degree of dilution, i.e. the free fraction increased significantly with increasing dilution (p < 0.0001). Furthermore, the binding was dependent on the total plasma concentration of lidocaine, since a significantly higher percentage of free drug was found at the higher total lidocaine level (4 μg/ml) compared with the lower level (1.5 μg/ml) (p < 0.05). No significant difference in the free fraction of lidocaine could be found over the studied haematocrit range. The results of the present study indicate that plasma protein levels commonly associated with CPB in neonates and infants are associated with a significant increase in the free, unbound and pharmacologically active fraction of lidocaine compared with normal conditions. The use of commonly recommended dosages of lidocaine might result in toxic-free concentration in this setting.

Influence of Maternal Plasma Protein Binding on Fetal Unbound Plasma Concentration of Propranolol in the Pregnant Ewe

1988 ◽  
Vol 77 (10) ◽  
pp. 835-837 ◽  
Author(s):  
Denis J. Morgan ◽  
George W. Mihaly ◽  
Mark A. Czuba ◽  
Michael S. Ching ◽  
Kenneth J. Hardy ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Maternal Plasma ◽  
Pregnant Ewe

Distribution, metabolism, excretion and toxicokinetics of vitexin in rats and dogs

2021 ◽  
Vol 17 ◽  
Author(s):  
Daopeng Tan ◽  
Geng Li ◽  
Wenying Lv ◽  
Xu Shao ◽  
Xiaoliang Li ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Intravenous Administration ◽  
Equilibrium Dialysis ◽  
Bioactive Compound ◽  
Repeated Administration ◽  
Time Curve ◽  
Suitable Alternative

Background: Vitexin is the main bioactive compound of hawthorn (Crataegus pinnatifida), a famous traditional Chinese medicine, and vitexin for injection is currently in phase I clinical trial in China. Objective: This investigation systematically evaluated the metabolism and toxicokinetics of vitexin in rats and dogs. Methods: Rats and beagle dogs were administrated different doses of vitexin, and then the plasma concentration, tissue distribution, excretion, metabolism, pharmacokinetics and plasma protein binding were investigated. Results : The elimination half-life (t1/2) values in rats after a single intravenous dose of 3, 15 and 75 mg/kg were estimated as 43.53±10.82, 22.86±4.23, and 21.17±8.64 min, and the values of the area under the plasma concentration-time curve (AUC0→∞) were 329.34±144.07, 974.79±177.27, and 5251.49±786.98 mg•min/L, respectively. The plasma protein binding rate in rats was determined as about 65% by equilibrium dialysis after 72 hr. After 24 hr of intravenous administration, 16.30%, 3.47% and 9.72% of the given dose were excreted in urine, feces and bile, respectively. The metabolites of the vitexin were hydrolyzed via deglycosylation. The pharmacokinetics of dogs after intravenous administration revealed t1/2, AUC0-∞ and mean residence time (MRT0-∞) values of 20.43±6.37 min, 227.96±26.68 mg•min/L and 17.12±4.33 min, respectively. The no-observed-adverse-effect level (NOAEL) was 50 mg/kg body weight/day. There was no significant accumulation effect at 8 or 20 mg/kg/day in dogs over 92 days of repeated administration. For the 50 mg/kg/day dose group, the exposure (AUC, Cmax) decreased significantly with prolonged administration. This trend suggests that repeated administration accelerates vitexin metabolism. Conclusion: The absorption of vitexin following routine oral administration was very low. To improve the bioavailability of vitexin, the development of an injectable formulation would be a suitable alternative choice.

The Effect of Age on the Pharmacokinetics of Diazepam

1980 ◽  
Vol 59 (6) ◽  
pp. 479-483 ◽  
Author(s):  
A. F. MacKlon ◽  
M. Barton ◽  
O. James ◽  
M. D. Rawlins
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Half Life ◽  
Free Fraction ◽  
The Elderly ◽  
Total Plasma ◽  
Increased Sensitivity ◽  
Plasma Half Life ◽  
Effect Of Age

1. After intravenous administration to 19 subjects, aged 18–95 years, plasma diazepam concentrations were measured over 160 h. Plasma protein binding of diazepam was also measured in each subject. 2. The terminal plasma half-life of diazepam ranged from 15.0 to 125 h and was positively correlated with age (r = 0.797). Total plasma diazepam clearance was not correlated with age (r = −0.017). 3. The free fraction of diazepam ranged from 0.0137 to 0.0386 and was significantly correlated with age (r = +0.863). Free diazepam clearance, which ranged from 432 to 1870 ml/min, was also correlated with age (r = −0.717). 4. It is concluded that the increased sensitivity of the elderly to diazepam is, at least in part, due to pharmacokinetic factors.

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