Biliary excretion of chenodeoxycholyllysylrhodamine in Wistar rats: a possible role of a bile acid as a carrier for drugs.
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.
Mills
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Department of Medicine, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK.
Elias
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D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004337:Drug Carriers; D006207:Half-Life; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012235:Rhodamines / Q000138:chemical synthesis / Q000378:metabolism* / Q000493:pharmacokinetics*
D001647:Bile Acids and Salts; D004337:Drug Carriers; D012235:Rhodamines; C075207:chenodeoxycholyllysylrhodamine; D002635:Chenodeoxycholic Acid