Effects of anemoside B4 on pharmacokinetics of florfenicol and mRNA expression of CXR, MDR1, CYP3A37 and UGT1E in broilers

J Vet Med Sci. 2019 Dec 26;81(12):1804-1809. doi: 10.1292/jvms.19-0293. Epub 2019 Oct 14.

Abstract

Pulsatillae radix, a traditional Chinese medicine (TCM), is often used in combination with florfenicol for treatment of intestinal infection in Chinese veterinary clinics. Anemoside B4 (AB4) is the major effective saponin in Pulsatillae radix. This study aimed to investigate whether the pharmacokinetics of florfenicol in broilers was affected by the combination of AB4. In this study, broilers were given AB4 (50 mg/kg BW), or 0.9% sodium chloride solution by oral administration for 7 days. They were then fed florfenicol orally (30 mg/kg BW) on the eighth day. The results showed that the AUC(0-∞), MRT(0-∞), t1/2z and Cmax of florfenicol were significantly decreased, and the Vz/F and CLz/F were significantly increased by AB4; the mRNA expression levels of CXR, CYP3A37 and MDR1 (except CXR and CYP3A37 in the liver) were up-regulated by AB4. In conclusion, AB4 altered the pharmacokinetics of florfenicol, resulting in lower plasma concentrations of florfenicol, this was probably related to the mRNA expression of CXR, CYP3A37 and MDR1 in the jejunum and liver (except CXR and CYP3A37) increased by AB4. The implications of these findings on the effect of traditional Chinese medicine containing AB4 on the effectiveness of florfenicol in veterinary practice deserve study.

Keywords: anemoside B4; drug-metabolizing enzyme; efflux transporter; florfenicol; pharmacokinetics.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Administration, Oral
  • Animals
  • Aryl Hydrocarbon Hydroxylases / genetics
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Avian Proteins / genetics
  • Avian Proteins / metabolism
  • Chickens
  • Cytochrome P450 Family 3 / genetics
  • Cytochrome P450 Family 3 / metabolism
  • Drug Interactions
  • Gene Expression / drug effects*
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism
  • Male
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Saponins / administration & dosage
  • Saponins / pharmacology*
  • Thiamphenicol / administration & dosage
  • Thiamphenicol / analogs & derivatives*
  • Thiamphenicol / blood
  • Thiamphenicol / pharmacokinetics

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Avian Proteins
  • CXR protein, chicken
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Saponins
  • anemoside B4
  • florfenicol
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P450 Family 3
  • cytochrome P-450 CYP3A37 (chicken)
  • Glucuronosyltransferase
  • Thiamphenicol