Influence of ion-pair formation on the pharmacokinetic properties of drugs. Pharmacokinetic interactions of bretylium and hexylsalicylic acid in rabbits.
The simultaneous i.v. administration of equimolar doses of bretylium and hexylsalicylic acid results in an increase in plasma area under the curve value of both substances in comparison with their separate administration. The higher plasma levels of both compounds were associated with a reduced renal excretion and an increased biliary elimination. However, the increase in biliary excretion did not compensate for the reduced elimination of bretylium and hexylsalicylic acid via the kidney. The results presented in this paper give further evidence that ion-pairing in-vivo may result in altered pharmacokinetics of drugs particularly due to changes in biliary or renal excretion.
Zentralinstitut für Mikrobiologie and Experimentelle Therapie, Jena, Germany.
R
R
Amlacher
A
A
Härtl
R
R
Neubert
U
U
Stöckel
K
K
Wenzel
D000818:Animals; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D001949:Bretylium Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004338:Drug Combinations; D005260:Female; D007275:Injections, Intravenous; D007477:Ions; D007668:Kidney / Q000378:metabolism; D008297:Male; D011817:Rabbits; D012459:Salicylates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D001949:Bretylium Compounds; D004338:Drug Combinations; D007477:Ions; D012459:Salicylates; C059285:3-hexylsalicylic acid; C045166:bretylium