Advertisement

European Journal of Clinical Pharmacology

, Volume 22, Issue 5, pp 451–457 | Cite as

Plasma protein binding of etidocaine during pregnancy and labour

  • D. J. Morgan
  • B. B. Koay
  • J. D. Paull
Originals

Summary

Preliminary studies of the ultrafiltration method for measuring the extent of plasma protein binding of etidocaine showed that etidocaine binding was both pH and concentration dependent. Etidocaine (1 µg/ml) was found to bind avidly to a physiological concentration (74 mg/dl) of α1-acid glycoprotein (α1-AGP) (7.23±0.64%, mean ± SD, unbound). In vitro investigation of etidocaine binding in plasma obtained from blood bank donors and from 19 pregnant women prior to induction of labour, during early labour, mid-labour and delivery showed no difference in etidocaine binding (10.3±3.3%, 7.06±2.66%, 8.15±2.57%, 7.84±3.74% and 9.28±6.06% unbound respectively). There was a significant increase in the mean plasma total free fatty acid (FFA) concentration from pre-labour (0.535±0.240 mM) to delivery (0.948±0.28 mM), while plasma albumin and β-lipoprotein concentrations remained constant. α1-Acid glycoprotein concentration tended to increase slightly from pre-labour to early labour (p<0.1) but was still within the normal physiological range. There was no correlation between etidocaine binding ratio and the concentrations of FFA or plasma proteins except for a poor correlation with the α1-AGP concentration (r=0.361, p<0.05). Storage of plasma and inadequate control of plasma pH during ultrafiltration appeared to give spurious binding values. These studies with the extensively bound basic drug etidocaine suggest that unlike many acidic drugs which are bound predominantly to serum albumin, the binding of α1-AGP — bound basic drugs may be unaffected by pregnancy and labour.

Key words

etidocaine protein binding pregnancy alpha1-acid glycoprotein labour free fatty acids 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bertilsson L, Braithwaite R, Tybring G, Garle M, Borga O (1979) Techniques for plasma protein binding of demethylchlorimipramine. Clin Pharmacol Ther 26:265–271Google Scholar
  2. 2.
    Burney RG, Difazio CA, Foster JA (1978) Effects of pH on protein binding of lidocaine. Anesth Analg 57:478–480Google Scholar
  3. 3.
    Burt RL (1960) Plasma nonesterified fatty acids in normal pregnancy and the puerperium. Obstet Gynecol 15:460–463Google Scholar
  4. 4.
    Crawford JS, Davies P, Davies P (1971) Further studies of the binding of bromsulphthalein by serum albumin. Br J Anaesth 43:344–351Google Scholar
  5. 5.
    Crawford JS, Hooi HW (1968) Binding of bromsulphthalein by serum albumin from pregnant women, neonates and subjects on oral contraceptives. Br J Anaesth 40:723–729Google Scholar
  6. 6.
    Csogor S, Csutak J, Pressler A (1969) Modifications of albumin in pregnant women and newborn infants. Biol Neonate 13:211–218Google Scholar
  7. 7.
    Dean M, Stock B, Patterson RJ, Levy G (1980) Serum protein binding of drugs during and after pregnancy in humans. Clin Pharmacol Ther 28:253–261Google Scholar
  8. 8.
    Koj A (1974) Acute-phase reactants. In: Allison AC (ed) Structure and function of plasma proteins, Vol 1. Plenum Press, LondonGoogle Scholar
  9. 9.
    Lovecchio JL, Krasner J, Yaffe SY (1981) Serum protein binding of salicylate during pregnancy and the puerperium. Dev Pharmacol Ther 2:172–179Google Scholar
  10. 10.
    Miller RG (1966) Simultaneous statistical inference. McGraw-Hill, New YorkGoogle Scholar
  11. 11.
    Morgan DJ, Cousins MJ, McQuillan D, Thomas J (1977) Disposition and placental transfer of etidocaine in pregnancy. Eur J Clin Pharmacol 12:359–365Google Scholar
  12. 12.
    Piafsky KM, Knoppert D (1978) Binding of local anesthetics to α1-acid glycoprotein. Clin Res 26:836AGoogle Scholar
  13. 13.
    Reboud P, Groulade J, Groslambert P, Colomb M (1963) The influence of normal pregnancy and the postpartum state on plasma proteins and lipids. Am J Obstet Gynecol 86:820–828Google Scholar
  14. 14.
    Ridd MJ, Nation RL, Brown KF, Moore RG, McBride WG (1980) Diazepam binding in the plasma of parturient women. Aust J Pharm Sci 9:56Google Scholar
  15. 15.
    Ruprah M, Perucca E, Richens A (1980) Decreased serum protein binding of phenytoin in late pregnancy. Lancet 1:316–317Google Scholar
  16. 16.
    Scheffé H (1959) The analysis of variance. John Wiley, New YorkGoogle Scholar
  17. 17.
    Skipski VP, Barclay M, Barclay RK, Fetzer VA, Good JJ, Archibald FM (1967) Lipid Composition of human serum lipoproteins. Biochem J 104:340–352Google Scholar
  18. 18.
    Tanaka FS, Wien RG (1973) Gas Chromatography of substituted phenylureas by Flash-Heater methylation with trismethylanilinium hydroxide. J Chromatogr. 87:85–93Google Scholar
  19. 19.
    Tucker GT and Mather LE (1975) Pharmacokinetics of local anaesthetic agents. Br J Anaesth 47:213–224Google Scholar
  20. 20.
    Vallner JJ, Chen L (1976) β-Lipoproteins: Possible plasma transport proteins for basic drugs. J Pharm Sci 65:420–421Google Scholar
  21. 21.
    Whaley WH, Zuspan FP, Nelson GH, Ahlquist RP (1967) Alterations of plasma free fatty acids and glucose during labour. Am J Obstet Gynecol 97:875–880Google Scholar

Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • D. J. Morgan
    • 1
  • B. B. Koay
    • 1
  • J. D. Paull
    • 2
  1. 1.Department of PharmaceuticsVictorian College of PharmacyMelbourneAustralia
  2. 2.The Royal Women's HospitalMelbourneAustralia

Personalised recommendations