Summary
The glucuronyltransferase activity towards morphine was measured in microsomes isolated from liver specimens obtained from human fetuses and cancer patients. All the fetal livers investigated had measurable UDP-glucuronyltransferase activity towards morphine. There was no correlation between the gestational age (15 to 27 weeks) and the glucuronidation rate. The mean value of the enzymatic activities was higher in fetal livers obtained by hysterotomy (0.20 nmoles×min−1×mg−1) than in livers obtained after induced abortion (0.11 nmoles×min−1×mg−1). The average rate of glucuronidation in microsomes from adult liver (mean 1.15 nmoles×mint-1×mg−1) was 6 to 10 times higher than in the fetal liver microsomes. Together with previous investigations on human adult and fetal liver glucuronidation, the present results support the theory of heterogeneity of human UDP-glucuronyltransferase.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bock KW, Brunner G, Hoensch H, Huber E and Joshing D (1978) Determination of microsomal UDP-glucuronyltransferase in needle-biopsy specimens of human liver. Eur J Clin Pharmacol 14: 367–373
Bock KW, Fröhling W, Remmer H, Rexer B (1973) Effects of phenobarbital and 3-methylcholantrene on substrate specificity of rat liver microsomal UDP-glucuronyltransferase. Biochim Biophys Acta 327: 46–56
Bock KW, von Clausbruch UC, Joshing D, Henwälder H (1977) Separation and partial purification of two differentially inducible UDP-glucuronyltransferases from rat liver. Biochem Pharmacol 26: 1097–1100
Del Villar E, Sanchez E, Tephly TR (1977) Morphine metabolism V. Isolation of separate glucuronyltransferase activities for morphine and p-nitrophenol from rabbit liver microsomes. Drug Metab Dispos 5: 273–278
Done AK (1964) Developmental pharmacology. Clin Pharmacol Ther 5: 432–479
Dvorchik BH, Stenger VG, Hartman RD (1979) Drug metabolism by the fetal stump-tailed monkey (Macaca arctoides). Pharmacology 18: 241–250
Garrettson LK, Procknal JA, Levy G (1975) Fetal acquisition and neonatal elimination of a large amount of salicylate. Clin Pharmacol Ther 17: 98–103
Hirvonen T (1966) In: Sarja-Series A. II. Biologica-Geographica, University of Turku, Finland.
Lathe GH, Walker M (1957) An enzyme defect in human neonatal jaundice and in Gunn's strain of jaundiced rats. Biochem J 67: 9
Levy G, Khanna NN, Soda DM, Tsuzuki O, Stern L (1975) Pharmacokinetics of acetaminophen in the human neonate: Formation of acetaminophen glucuronide and sulfate in relation to plasma bilirubin concentration and d-glucaric acid excretion. Pediatrics (Springfield) 55: 818–825
Miller RP, Roberts RJ, Fischer LJ (1976) Acetaminophen elimination kinetics in neonates, children and adults. Clin Pharmacol Ther 19: 284–294
Onishi S, Kawade N, Itoh S, Isobe K, Sugiyama S (1979) Postnatal development of uridine diphosphate glucuronyltransferase activity towards bilirubin and 2-aminophenol in human liver. Biochem J 184: 795–807
Pacifici GM, Rane A (1981) Inhibition of morphine glucuronidation by oxazepam in human fetal liver microsomes. Drug Metab Dispos 9: 569–572
Pelkonen O, Vorne M, Kärki NT (1969) Drug-metabolizing activity in the liver, intestine and kidney of human foetus. Acta Physiol Scand 77 (Suppl 330): 69
Rane A (1973) Academic Thesis. Karolinska Institute. Nordstedt and Sons, Stockholm
Rane A, Sjöqvist F, Orrenius S (1973) Drugs and fetal metabolism. Clin Pharmacol Ther 14: 666–672
Rollins D, von Bahr C, Glaumann H, Moldéus P, Rane A (1979) Acetaminophen: Reactive intermediate formation by human and adult liver microsomes and isolated fetal liver cells. Science 205: 1414–1416
Schoene B, Fleishmann KA, Remmer H, von Oldershausen HF (1972) Determination of drug metabolizing enzymes in needle biopsies of human liver. Eur J Clin Pharmacol 4: 65–73
Steiner E, von Bahr C, Rane A (1982) Sulphate and glucuronic acid conjugation of harmol on human fetal and adult liver. Dev Pharmacol ther (In press)
Säwe J, Pacifici GM, Kager L, von Bahr C, Rane A (1982) Glucuronidation of morphine in human liver and interaction with oxazepam. Acta Anaesthesiol Scand (Suppl 74): 47–51
Tomson G, Sundwall A, Lunell N-O, Rane A (1979) Transplacental passage and kinetics in the mother and newborn of oxazepam given during labor. Clin Pharmacol Ther 25: 74–81
Wishart GJ, Dutton GJ (1978) Inducation by Natural and Xenobiotic Compounds of UDP-Glucuronyl-Transferase. Activities During the Perinatal Period. In: Neubert D, Merker H-J, Nau H, Langman J (eds) Role of pharmacokinetics in prenatal and perinatal toxicology. Thieme, Stuttgart, pp 215–224
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pacifici, G.M., Säwe, J., Kager, L. et al. Morphine glucuronidation in human fetal and adult liver. Eur J Clin Pharmacol 22, 553–558 (1982). https://doi.org/10.1007/BF00609630
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00609630