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PubMed1984

Structure-pharmacokinetics relationship of quaternary ammonium compounds. Elimination and distribution characteristics.

The pharmacokinetics of a series of fourteen monoquaternary ammonium ions, with gradually increasing molecular weight, were studied in anaesthetized rats after intravenous bolus injection and/or constant infusion. Distribution to the eliminating organs and elimination rate into bile, urine and intestinal lumen as well as the plasma disappearance were investigated. All compounds showed a double exponential plasma disappearance pattern. Initial half lives (alpha-phase) varied between 0.5 and 3 min, half lives of the beta-phase varied between 30 and 70 min. Total plasma clearance within the series of compounds ranges from 2.3-13.7 ml/min, in general increasing with molecular weight. The relative contribution of biliary, urinary, and intestinal elimination to the total plasma clearance varied widely within the series of organic cations. Renal clearance of all the compounds exceeded that of mannitol, indicating involvement of active renal transport processes. Excretion via the kidneys was the only important excretory pathway for compounds with molecular weights less than 156. The low biliary excretion of the compounds of M less than 156 was not due to a deficient hepatic penetration since uptake into the liver was very rapid. Only the high molecular weight compounds (greater than 156) showed a profound bile/plasma concentration ratio ranging from 13 to 830. For these compounds also an "uphill" excretion process into the gut lumen seems to be involved representing up to 15% of the administered dose. It is concluded that elimination patterns for organic cations of various structure differ much more than their overall distribution characteristics.

Animals↗