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Drug distribution in whole blood of mothers and their newborn infants

Studies of cloxacillin and flucloxacillin

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Summary

The distribution of cloxacillin and flucloxacillin in whole blood from seven newborn infants and their mothers was determined in vitro by equilibrium dialysis at 37°C. Seven healthy, non-pregnant women of reproductive age served as controls. The distribution of the penicillins to erythrocytes was the same in the infants as in the adults. It was significantly lower in the presence of plasma albumin than when plasma was replaced by isotonic phosphate buffer. The plasma protein binding of cloxacillin and flucloxacillin in 22 infants was significantly lower than in the controls, but was slightly higher than in the mothers. A significant correlation between binding of cloxacillin and flucloxacillin in the same individual suggested that the two drugs were bound to similar sites. During the first postnatal week binding in infant plasma decreased. This change was correlated with an increase in the bilirubin levels. In the mothers, the binding increased during the first week after delivery. On the basis of the distribution data, maternal to fetal plasma and whole blood concentration ratios at equilibrium were calculated. These ratios were lower for flucloxacillin (medians 0.770 and 0.821, respectively) than for cloxacillin 0.996 and 1.094). Accordingly, at equilibrium somewhat higher levels of flucloxacillin should appear on the fetal than on the maternal side, whereas the concentrations of cloxacillin would be expected to be approximately the same.

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References

  1. Gleichmann W, Bachmann GW, Dengler HJ, Dudeck J (1973) Effects of hormonal contraceptives and pregnancy on serum protein pattern. Eur J Clin Pharmacol 5: 218–225

    Google Scholar 

  2. Krauer B, Krauer F, Hytten FE (1980) Drug disposition and pharmacokinetics in the maternal-placental-fetal unit. Pharmacol Ther 10: 301–328

    Google Scholar 

  3. Dubowitz L, Dubowitz V, Goldberg C (1970) Clinical assessment of gestational age in the newborn infant. J Pediatr 77: 1

    Google Scholar 

  4. McArthur JN, Dawkins P, Smith MJ (1971) The binding of indomethacin, salicylate and phenobarbitone to human whole blood in vitro. J Pharm Pharmacol 23: 32–36

    Google Scholar 

  5. Ehrnebo M, Odar-Cederlöf I (1975) Binding of amobarbital, pentobarbital and diphenylhydantoin to blood cells and plasma proteins in healthy volunteers and uraemic patients. Eur J Clin Pharmacol 8: 445–453

    Google Scholar 

  6. Jalling B, Malmborg AS, Lindman A, Boréus LO (1972) Evaluation of a micromethod for determination of antibiotic concentrations in plasma. Eur J Clin Pharmacol 4: 150–157

    Google Scholar 

  7. Ehrnebo M, Agurell S, Boréus LO, Gordon E, Lönroth U (1974) Pentazocine binding to blood cells and plasma proteins. Clin Pharmacol Ther 16: 424–429

    Google Scholar 

  8. Bergström K, Lefwert AK (1980) An automatical turbidimetric immunoassay for plasma proteins. Scand J Clin Lab Invest 40: 637–641

    Google Scholar 

  9. Michaelsson M (1972) Evaluation of a method for determination of bilirubin in serum using direct spectrophotometry. Scand J Clin Lab Invest 30: 387–390

    Google Scholar 

  10. Kendall MG (1970) Rank correlation methods, 4th edn. Griffin, London

    Google Scholar 

  11. Schanker LS, Johnson JM, Jeffrey JY (1964) Rapid passage of organic anions into human red cells. Am J Physiol 207: 503–508

    Google Scholar 

  12. Meyer MC, Guttman DE (1968) The binding of drugs by plasma proteins. J Pharm Sci 57: 895–918

    Google Scholar 

  13. Koch-Weser J, Sellers ED (1976) Binding of drugs to serum albumin. N Engl J Med 294 10: 526–531

    Google Scholar 

  14. Ehrnebo M, Agurell S, Jalling B, Boréus LO (1971) Age differences in drug binding by plasma proteins. Eur J Clin Pharmacol 3: 189–193

    Google Scholar 

  15. Krasner J, Yaffe SJ (1975) Drug-protein binding in the neonate. In: Morselli PL, Garattini S and Sereni F (eds) Basic and therapeutic aspects of perinatal pharmacology. Raven Press, New York, pp 357–366

    Google Scholar 

  16. Ganzhorn A, Kurz H (1968) Unterschiede zwischen der Proteinbindung Neugeborener und Erwachsener und ihre Bedeutung für die pharmakologische Wirkung. Naunyn Schmiedeberg's Arch Pharmacol 260: 117–118

    Google Scholar 

  17. Levy G, Prochnal JA, Garrettson LK (1975) Distribution of salicylate between neonatal and maternal serum at diffusion equilibrium. Clin Pharmacol Ther 18: 210–214

    Google Scholar 

  18. Rane A, Lunde PKM, Jalling B, Yaffe SJ, Sjöqvist F (1971) Plasma protein binding of diphenylhydantoin in normal and hyperbilirubinemic infants. J Pediatr 78: 877–882

    Google Scholar 

  19. Bratlid D (1976) Pharmacologic aspects of neonatal hyperbilirubinemia. Birth Defects Orig Artic Ser 2: 184–189

    Google Scholar 

  20. Kornguth ML, Kunin CM (1976) Binding of antibiotics to the human intracellular erythrocyte proteins hemoglobin and carbonic anhydrase. J Infect Dis 133: 185–193

    Google Scholar 

  21. Kornguth ML, Kunin CM (1976) Uptake of antibiotics by human erythrocytes. J Infect Dis 133: 175–184

    Google Scholar 

  22. Gorodischer R, Jusko WJ, Yaffe SJ (1975) Tissue and erythrocyte distribution of digoxin in infants. Clin Pharmacol Ther 19: 256–263

    Google Scholar 

  23. Ehrnebo M, Nilsson SO, Boréus LO (1979) Pharmacokinetics of ampicillin and its pro-drugs bacampicillin and pivampicillin in man. J Pharmacokinet Biopharm 7: 429–451

    Google Scholar 

  24. Honig GR, Hruby M (1977) Disorders of the vessel and hematopoetic system. In: Behrman RE (ed) Neonatal-perinatal medicine, 2nd edn. Mosby, Saint Louis, pp 345–393

    Google Scholar 

  25. Yaffe SJ, Boréus LO (1972) Fetal pharmacology. In: Barnett HL, Einhorn AH (eds) Pediatrics, 15th edn. Appleton-Century-Crofts, New York, pp 51–56

    Google Scholar 

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Herngren, L., Ehrnebo, M. & Boréus, L.O. Drug distribution in whole blood of mothers and their newborn infants. Eur J Clin Pharmacol 22, 351–358 (1982). https://doi.org/10.1007/BF00548405

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  • DOI: https://doi.org/10.1007/BF00548405

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