Biliary excretion of chenodeoxycholyllysylrhodamine in Wistar rats: a possible role of a bile acid as a carrier for drugs

Biochim Biophys Acta. 1992 Jun 5;1126(1):35-40. doi: 10.1016/0005-2760(92)90213-f.

Abstract

The effect on biliary excretion of rhodamine after its conjugation to give chenodeoxycholyl-lysyl-rhodamine (cheno-lys-R) was studied in male Wistar rats. Following its intravenous injection via the jugular vein of animals cheno-lys-R was efficiently excreted into bile with a peak biliary excretion of 31.6 +/- 1.2% dose 5 min-1 and a cumulative biliary excretion of 96.4 +/- 2.0% in 30 min of the total dose administered. Unlike cheno-lys-R, rhodamine had a poor biliary excretion of 1.0 +/- 0.1% dose 5 min-1 and a cumulative biliary excretion of 3.3 +/- 0.6% in 30 min. Cheno-lys-R had a short plasma half-life (t1/2 alpha) of 4.0 +/- 0.5 min, whereas free rhodamine had a longer half life (t1/2 alpha) of 82.1 +/- 1.4 min. The plasma clearances of cheno-lys-R and rhodamine were 41.2 +/- 6.5 and 9.0 +/- 1.2 ml/min per kg, respectively. The data indicate that the cationic fluorescent xenobiotic, rhodamine, when conjugated to the bile salt analogue, greatly increased the biliary excretion of rhodamine and that cheno-lys acted as a carrier for hepatic uptake of rhodamine. Thus, an appropriate bile salt derivative may be used to target a drug to the liver.

MeSH terms

  • Animals
  • Bile / metabolism*
  • Bile Acids and Salts*
  • Chenodeoxycholic Acid / analogs & derivatives*
  • Chenodeoxycholic Acid / chemical synthesis
  • Chenodeoxycholic Acid / pharmacokinetics
  • Drug Carriers
  • Half-Life
  • Male
  • Rats
  • Rats, Inbred Strains
  • Rhodamines / chemical synthesis
  • Rhodamines / metabolism*
  • Rhodamines / pharmacokinetics*

Substances

  • Bile Acids and Salts
  • Drug Carriers
  • Rhodamines
  • chenodeoxycholyllysylrhodamine
  • Chenodeoxycholic Acid