Diazepam plasma binding in the perinatal period

Influence of nonesterified fatty acids

M. J. Ridd, K. F. Brown, R. G. Moore, W. G. McBride, R. L. Nation

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)153-160
Number of pages8
JournalEuropean Journal of Clinical Pharmacology
Volume22
Issue number2
DOIs
Publication statusPublished - 1 Mar 1982

Keywords

  • alpha-1-acid glycoprotein concentrations
  • diazepam
  • perinatal period
  • plasma NEFA concentration
  • regression analyses

Cite this

Ridd, M. J. ; Brown, K. F. ; Moore, R. G. ; McBride, W. G. ; Nation, R. L. / Diazepam plasma binding in the perinatal period : Influence of nonesterified fatty acids. In: European Journal of Clinical Pharmacology. 1982 ; Vol. 22, No. 2. pp. 153-160.
@article{83c528b3f1f941ec9dd04339ff2271dd,
title = "Diazepam plasma binding in the perinatal period: Influence of nonesterified fatty acids",
abstract = "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.",
keywords = "alpha-1-acid glycoprotein concentrations, diazepam, perinatal period, plasma NEFA concentration, regression analyses",
author = "Ridd, {M. J.} and Brown, {K. F.} and Moore, {R. G.} and McBride, {W. G.} and Nation, {R. L.}",
year = "1982",
month = "3",
day = "1",
doi = "10.1007/BF00542461",
language = "English",
volume = "22",
pages = "153--160",
journal = "European Journal of Clinical Pharmacology",
issn = "0031-6970",
publisher = "Springer-Verlag London Ltd.",
number = "2",

}

Diazepam plasma binding in the perinatal period : Influence of nonesterified fatty acids. / Ridd, M. J.; Brown, K. F.; Moore, R. G.; McBride, W. G.; Nation, R. L.

In: European Journal of Clinical Pharmacology, Vol. 22, No. 2, 01.03.1982, p. 153-160.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Diazepam plasma binding in the perinatal period

T2 - Influence of nonesterified fatty acids

AU - Ridd, M. J.

AU - Brown, K. F.

AU - Moore, R. G.

AU - McBride, W. G.

AU - Nation, R. L.

PY - 1982/3/1

Y1 - 1982/3/1

N2 - 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.

AB - 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.

KW - alpha-1-acid glycoprotein concentrations

KW - diazepam

KW - perinatal period

KW - plasma NEFA concentration

KW - regression analyses

UR - http://www.scopus.com/inward/record.url?scp=0020073979&partnerID=8YFLogxK

U2 - 10.1007/BF00542461

DO - 10.1007/BF00542461

M3 - Article

VL - 22

SP - 153

EP - 160

JO - European Journal of Clinical Pharmacology

JF - European Journal of Clinical Pharmacology

SN - 0031-6970

IS - 2

ER -