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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Analytical chemistry 49 (1977), S. 2023-2030 
    ISSN: 1520-6882
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 27 (1984), S. 459-463 
    ISSN: 1432-1041
    Keywords: naloxone ; plasma protein binding ; albumin ; alpha1-acid glycoprotein ; beta-lipoprotein ; adult plasma ; foetal/umbilical plasma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Binding of naloxone hydrochloride was determined at 37°C, by equilibrium dialysis against 0.067 M phosphate buffer, pH 7.4, in plasma obtained from 18 healthy adults, and 18 samples of umbilical cord venous (foetal) plasma. The percentage free fraction (% free) in plasma was independent of naloxone concentration (9 ng/ml to 2.5 µg/ml). Percent free naloxone in adult (x=54.0) was lower (p〈0.01) than in foetal (x=61.5) plasma. In buffered solutions of purified HSA, %free naloxone (x=68.7) was independent of HSA concentration over the range 3.0 g/dl to 5.5 g/dl. Adult plasma concentrations of α1-acid glycoprotein (α1-AGP) and β-lipoprotein were higher (p〈0.01) than foetal concentrations. Furthermore %free naloxone in foetal plasma decreased with the in-vitro addition of purified α1-AGP. It is suggested that qualitative differences in adult and foetal albumin and quantitative differences in plasma levels of α1-AGP and perhaps β-lipoprotein are responsible for naloxone plasma binding differences between adults and the newborn.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 243-250 
    ISSN: 1432-1041
    Keywords: pancuronium ; neuromuscular relaxants ; simultaneous modelling ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of pancuronium were studied following intravenous infusion in eleven patients undergoing surgical anaesthesia. Measurement of the plasma concentrations (Cp) of the neuromuscular blocking agent (NMBA) and the concomitant intensities of paralysis allowed their simultaneous modelling. The pharmacokinetic parameters derived for pancuronium were in the range of previously reported values, except that the mean total systemic plasma clearance (0.79±0.28 ml·min−1·kg−1) was reduced and the mean terminal phase half-life (169 min) was longer in these patients. Plasma concentration and % paralysis data were successfully fitted to a previously proposed pharmacodynamic model. This model assumes a separate effect compartment which exchanges drug directly with the central kinetic compartment (integrated effect model). The ‘steady-state’ Cp necessary to produce 50% paralysis (ECpss(50)) was estimated to be 0.21±0.08 µg·ml−1 (mechanical response) and 0.18±0.05 µg·ml−1 (EMG response). An analysis using the Hill equation of the Cp-response relationship, during and after the constantrate infusion of pancuronium bromide, resulted in effective plasma concentrations for 50% paralysis (ECp50) of 0.35±0.06 µg·ml−1 and 0.20±0.09 µg·ml−1, respectively, for mechanical twitch response. The corresponding values for EMG response were 0.32±0.06 µg·ml−1 and 0.17±0.06 µg·ml−1. Using this latter approach, the ECp50 estimated during onset of paralysis was significantly higher than that estimated during offset of paralysis (p〈0.05); no such difference was apparent between this latter parameter and the ECpss(50) of the integrated effect model (p〉0.05). No significant differences were observed between any of the pharmacodynamic parameter estimates generated from the data obtained from the two methods of assessment of neuromuscular function (mechanical vs. EMG response) (p〉0.05).
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 479-481 
    ISSN: 1432-1041
    Keywords: plasma protein binding ; ritodrine hydrochloride ; albumin binding ; alpha1-acid glycoprotein ; parturition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The binding of ritodrine HCl in whole plasma from healthy nonpregnant women, parturients and matched umbilical venous plasma and in solutions of HSA and α1-AGP has been studied by equilibrium dialysis. Binding to plasma from nonpregnant subjects and HSA was independent of ritodrine concentration over a wide range. The free fraction in plasma was high and significantly different between groups of nonpregnant (α=0.64), parturient (α=0.68) and matched umbilical venous plasma (α=0.75). It would seem that variability in transplacental transfer of ritodrine, as a result of plasma binding fluctuations, will be minor.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 22 (1982), S. 153-160 
    ISSN: 1432-1041
    Keywords: diazepam ; perinatal period ; plasma NEFA concentration ; regression analyses ; alpha-1-acid glycoprotein concentrations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma binding of diazepam was determined serially in 24 women undergoing either elective induction of labour (vaginal or emergency caesarean delivery) or elective caesarean section at term and in 5 nonpregnant women requiring abdominal surgery. In the majority of pregnant patients, a marked increase in diazepam percentage free was observed during labour or prior to caesarean section, reaching a maximum, 1.6 to 3.2 fold increase at delivery or within 4 h postpartum; by the fifth day postpartum, diazepam percentage free was lower than on admission to hospital. In contrast, little change in diazepam percentage free was observed during the perisurgical period in nonpregnant patients. In parturient and surgical patients, the time courses of diazepam percentage free and plasma nonesterified fatty acid (NEFA) concentration were parallel. Bivariate regression analyses of pooled data demonstrated a strong correlation (r=0.642, p=〈0.01) between diazepam percentage free and corresponding NEFA concentration and a weaker correlation between diazepam percentage free and both albumin (r=−0.319, p〈0.02) or total protein (r=−0.438, p〈0.01). From multiple linear regression it was demonstrated that 54% of the variability in diazepam percentage free could be attributed to plasma NEFA and albumin concentrations. NEFA displacement of plasma bound diazepam was substantiated using crystalline human serum albumin. An approximate 65% increase in plasma α1acid glycoprotein levels was observed posttrauma in both parturient and surgical patients but was unrelated to diazepam binding events. A relationship between diazepam plasma binding changes and concurrently altered disposition of diazepam during parturition is postulated.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 24 (1983), S. 595-601 
    ISSN: 1432-1041
    Keywords: diazepam ; fatty acid binding ; matched maternal and foetal plasma ; plasma NEFA concentration ; plasma bilirubin ; plasma albumins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Diazepam plasma binding was determined in 17 matched pairs of maternal and foetal plasma, collected at delivery. Diazepam % free was higher (p〈0.001) in maternal (mean 3.24%) than in either umbilical venous (mean 1.50%) or umbilical arterial (mean 1.24%) plasma. The data from in vitro dialysis studies were consistent with the reported higher diazepam concentrations in infants than in mothers at delivery. Plasma nonesterified fatty acids (NEFA) concentrations were higher (p〈0.001) in maternal (x = 643 μM) than in matched umbilical venous plasma (x = 211 μM) and there was a significant correlation (p〈0.01) between diazepam % free and corresponding plasma NEFA concentration for pooled data (r=0.871, n=34). Multiple and partial regression analysis indicates that transplacental differences in albumin, bilirubin and total protein concentrations made a minimal contribution to diazepam binding differences between mother and foetus and that approximately 76% of the variability in diazepam % free was accounted for by plasma NEFA concentration. The binding of diazepam to human serum albumin (HSA) was markedly perturbed by the presence of NEFA but not by bilirubin and there was no apparent cooperativity between bilirubin and NEFA on diazepam-HSA binding. Moreover, our findings provide further evidence that substantial differences in binding affinities exist between foetal and maternal plasma albumins.
    Type of Medium: Electronic Resource
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