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
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
Krauer B, Krauer F, Hytten FE (1980) Drug disposition and pharmacokinetics in the maternal-placental-fetal unit. Pharmacol Ther 10: 301–328
Dubowitz L, Dubowitz V, Goldberg C (1970) Clinical assessment of gestational age in the newborn infant. J Pediatr 77: 1
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
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
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
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
Bergström K, Lefwert AK (1980) An automatical turbidimetric immunoassay for plasma proteins. Scand J Clin Lab Invest 40: 637–641
Michaelsson M (1972) Evaluation of a method for determination of bilirubin in serum using direct spectrophotometry. Scand J Clin Lab Invest 30: 387–390
Kendall MG (1970) Rank correlation methods, 4th edn. Griffin, London
Schanker LS, Johnson JM, Jeffrey JY (1964) Rapid passage of organic anions into human red cells. Am J Physiol 207: 503–508
Meyer MC, Guttman DE (1968) The binding of drugs by plasma proteins. J Pharm Sci 57: 895–918
Koch-Weser J, Sellers ED (1976) Binding of drugs to serum albumin. N Engl J Med 294 10: 526–531
Ehrnebo M, Agurell S, Jalling B, Boréus LO (1971) Age differences in drug binding by plasma proteins. Eur J Clin Pharmacol 3: 189–193
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
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
Levy G, Prochnal JA, Garrettson LK (1975) Distribution of salicylate between neonatal and maternal serum at diffusion equilibrium. Clin Pharmacol Ther 18: 210–214
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
Bratlid D (1976) Pharmacologic aspects of neonatal hyperbilirubinemia. Birth Defects Orig Artic Ser 2: 184–189
Kornguth ML, Kunin CM (1976) Binding of antibiotics to the human intracellular erythrocyte proteins hemoglobin and carbonic anhydrase. J Infect Dis 133: 185–193
Kornguth ML, Kunin CM (1976) Uptake of antibiotics by human erythrocytes. J Infect Dis 133: 175–184
Gorodischer R, Jusko WJ, Yaffe SJ (1975) Tissue and erythrocyte distribution of digoxin in infants. Clin Pharmacol Ther 19: 256–263
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
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
Yaffe SJ, Boréus LO (1972) Fetal pharmacology. In: Barnett HL, Einhorn AH (eds) Pediatrics, 15th edn. Appleton-Century-Crofts, New York, pp 51–56
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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