Relationship between the transplacental gradients of bupivacaine and alpha 1‐acid glycoprotein.

Petersen, MC; Moore, R. G.; Nation, RL; McMeniman, W. J.

doi:10.1111/j.1365-2125.1981.tb01321.x

Cited by 30 publications

(5 citation statements)

References 15 publications

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“…This is due in part to the maternal state of hypoalbuminaemia, but the fetal concentration is still less than that in the average non-pregnant adult. In contrast, term fetal aI-acid glycoprotein plasma concentrations are only 30 to 40% of maternal concentrations (Petersen et al 1981;Wood & Wood 1981). During the first week of life neonatal aI-acid glycoprotein levels double, thus approaching adult concentrations (Philip & Hewitt 1983).…”

Section: Factors Affecting Maternal and Fetal Plasma Protein Bindingmentioning

confidence: 81%

The Significance of Plasma Protein Binding on the Fetal/Maternal Distribution of Drugs at Steady-State

Hill

Abramson

1988

Clinical Pharmacokinetics

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Maternal and fetal plasma differ in their concentrations of the important drug binding plasma proteins, albumin and alpha 1-acid glycoprotein, with albumin being slightly more concentrated in fetal plasma, and alpha 1-acid glycoprotein being only 37% of the maternal concentration at term. In general, these differences relate linearly to the bound to free concentration ratio of drugs associated with these proteins. Although only the free concentration is generally considered to be the pharmacologically active form, these differences can dramatically affect the total concentration and relative distribution of drugs between maternal and fetal plasma. In order to test our hypothesis that plasma protein binding is the major determinant of fetal/maternal drug distribution at steady-state, we examined whether fetal binding could be predicted from adult binding information. Data from studies of maternal plasma protein binding were used to predict fetal plasma protein binding based solely on the differences in protein concentrations. These predictions were compared with observed fetal binding data. This analysis showed a slope near unity and a high correlation (r2 = 0.900) which implies that there are no significant differences between the binding affinities of these proteins. A similar analysis performed using data on drug binding in non-pregnant adults gave an r2 or 0.971. Having established that fetal plasma proteins bind drugs similarly to their maternal counterparts, fetal/maternal plasma drug concentration ratios (F/M) were predicted for various drugs using information from literature on the drug's adult plasma protein binding, the protein to which it binds, and the fetal and maternal plasma concentrations of that binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Factors Affecting Maternal and Fetal Plasma Protein Bindingmentioning

confidence: 81%

The Significance of Plasma Protein Binding on the Fetal/Maternal Distribution of Drugs at Steady-State

Hill

Abramson

1988

Clinical Pharmacokinetics

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“…There is no evidence from this study to support the theory that low fetal: maternal ratios of bupivacaine are caused by extensive fetal tissue uptake [16]. Low feto: maternal ratios are predominantly the effect of differences in o^-acid glycoprotein concentrations [17].…”

Section: Discussionmentioning

confidence: 58%

Effect of Adrenaline on the Distribution of Bupivacaine in the Rabbit Fetus

Laishley

Carson

Reynolds

1989

British Journal of Anaesthesia

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Adrenaline may decrease uterine blood flow and influence transplacental distribution of bupivacaine. Sixteen pregnant rabbits received an i.v. infusion of 0.125% bupivacaine either plain (n = 8) or with adrenaline 1.25 microgram ml-1. At 15-min intervals following the start of the infusion, rabbit fetuses were removed serially and bupivacaine concentrations measured in maternal arterial plasma, fetal plasma and brain, amniotic fluid and placenta. The presence of adrenaline was associated with increased bupivacaine concentration in placenta; there was no other significant effect on fetal bupivacaine concentrations or ratios. Fetal:maternal plasma ratios increased (P less than 0.05), while fetal brain:fetal plasma ratios decreased (P less than 0.05) significantly with time.

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“…As gestation progresses, α1-acid glycoprotein plasma concentration decreases [37]. Since only protein-unbound drugs are available to cross the placenta, the lower α1-acid glycoprotein levels in pregnant women at term implicate a higher unbound fraction of bupivacaine and, consequently, in a higher placental transfer [38,39]. In this context, Tsen et al [37] demonstrated that an increase in the free fraction of bupivacaine was observed with increasing gestational age and with decreasing α-1 acid glycoprotein plasma concentration [37].…”

Section: Discussionmentioning

confidence: 99%

Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus‐infected pregnant women

Ribeiro

Moreira

Moisés

et al. 2018

Brit J Clinical Pharma

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Relationship between the transplacental gradients of bupivacaine and alpha 1‐acid glycoprotein.

Cited by 30 publications

References 15 publications

The Significance of Plasma Protein Binding on the Fetal/Maternal Distribution of Drugs at Steady-State

The Significance of Plasma Protein Binding on the Fetal/Maternal Distribution of Drugs at Steady-State

Effect of Adrenaline on the Distribution of Bupivacaine in the Rabbit Fetus

Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus‐infected pregnant women

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