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Influence of human recombinant interleukin-1ß on the enantioselective disposition of propranolol in rats

(1993) BIOCHEMICAL PHARMACOLOGY. 45(1). p.1-6
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Abstract
The influence of i.v. administration of 10 mug/kg recombinant human interleukin-1beta (rhIL-1beta), a putative mediator of inflammation, on the pharmacokinetics and metabolism of the propranolol enantiomers was studied in rats aged 3, 12 and 24 months. After oral administration of rac-propranolol to control rats of the three age groups, the plasma concentrations of (R)-propranolol were higher than those of (S)-propranolol. Administration of IL-1beta increased the plasma concentrations of the (R)-enantiomer markedly and significantly, those of the (S)-enantiomer only to a lesser degree. For both enantiomers an important increase in plasma binding was found in the IL-1beta-treated rats, which was linked to the increase in alpha1-acid glycoprotein levels. The in vitro clearance, measured in 3-month-old rats using the 9000 g liver fraction, was for neither of the propranolol enantiomers influenced by IL-1beta treatment, which is in keeping with the unchanged cytochrome P450 content. The enantioselective influence of IL-1beta treatment on the pharmacokinetics of propranolol was also present in 12- and 24-month-old rats, although somewhat less pronounced in the latter group. Our results show an enantioselective influence of IL-1beta treatment on the pharmacokinetics of propranolol in the rat, favouring the (R)-enantiomer.
Keywords
CLEARANCE, KINETICS, INFLAMMATION, PHARMACOKINETICS, CYTOCHROME-P-450, SERUM, ANTIPYRINE, METABOLISM, ALPHA-1-ACID GLYCOPROTEIN, PROTEIN BINDING

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Citation

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Chicago
Vermeulen, An, Frans Belpaire, Frits De Smet, and Marcus Bogaert. 1993. “Influence of Human Recombinant Interleukin-1ß on the Enantioselective Disposition of Propranolol in Rats.” Biochemical Pharmacology 45 (1): 1–6.
APA
Vermeulen, An, Belpaire, F., De Smet, F., & Bogaert, M. (1993). Influence of human recombinant interleukin-1ß on the enantioselective disposition of propranolol in rats. BIOCHEMICAL PHARMACOLOGY, 45(1), 1–6.
Vancouver
1.
Vermeulen A, Belpaire F, De Smet F, Bogaert M. Influence of human recombinant interleukin-1ß on the enantioselective disposition of propranolol in rats. BIOCHEMICAL PHARMACOLOGY. 1993;45(1):1–6.
MLA
Vermeulen, An, Frans Belpaire, Frits De Smet, et al. “Influence of Human Recombinant Interleukin-1ß on the Enantioselective Disposition of Propranolol in Rats.” BIOCHEMICAL PHARMACOLOGY 45.1 (1993): 1–6. Print.
@article{200562,
  abstract     = {The influence of i.v. administration of 10 mug/kg recombinant human interleukin-1beta (rhIL-1beta), a putative mediator of inflammation, on the pharmacokinetics and metabolism of the propranolol enantiomers was studied in rats aged 3, 12 and 24 months. After oral administration of rac-propranolol to control rats of the three age groups, the plasma concentrations of (R)-propranolol were higher than those of (S)-propranolol. Administration of IL-1beta increased the plasma concentrations of the (R)-enantiomer markedly and significantly, those of the (S)-enantiomer only to a lesser degree. For both enantiomers an important increase in plasma binding was found in the IL-1beta-treated rats, which was linked to the increase in alpha1-acid glycoprotein levels. The in vitro clearance, measured in 3-month-old rats using the 9000 g liver fraction, was for neither of the propranolol enantiomers influenced by IL-1beta treatment, which is in keeping with the unchanged cytochrome P450 content. The enantioselective influence of IL-1beta treatment on the pharmacokinetics of propranolol was also present in 12- and 24-month-old rats, although somewhat less pronounced in the latter group. Our results show an enantioselective influence of IL-1beta treatment on the pharmacokinetics of propranolol in the rat, favouring the (R)-enantiomer.},
  author       = {Vermeulen, An and Belpaire, Frans and De Smet, Frits and Bogaert, Marcus},
  issn         = {0006-2952},
  journal      = {BIOCHEMICAL PHARMACOLOGY},
  language     = {eng},
  number       = {1},
  pages        = {1--6},
  title        = {Influence of human recombinant interleukin-1{\ss} on the enantioselective disposition of propranolol in rats},
  url          = {http://dx.doi.org/10.1016/0006-2952(93)90369-8},
  volume       = {45},
  year         = {1993},
}

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