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British Journal of Anaesthesia, 1985, Vol. 57, No. 10 1012-1017
© 1985 The Board of Management and Trustees of the British Journal of Anaesthesia

research-article

pH-DEPENDENT ACCUMULATION OF FENTANYL, LOFENTANIL AND ALFENTANIL BY BEATING GUINEAPIG ATRIA

H. LÜLLMANN, M.D., B.-S. MARTINS and T. PETERS, M.D.

Department of Pharmacology, University of Kiel Hospitalstrasse 4-6, 2300 Kiel, West Germany.

The influence of the pH of the incubation medium on the cellular accumulation of tritiated fentanyl, lofentanil, and alfentanil was investigated in isolated guineapig atria. Fentanyl and lofentanil accumulated in atrial tissue up to about 30- and 50-fold, respectively. The amount of drug bound when equilibrium was attained was found to be dependent upon the pH of the medium. By plotting binding equilibria v. pH of the bath, curves were obtained which resembled titration curves. Half-maximal binding was attained at pH values close to the pKa values of fentanyl and lofentanil. Alfentanil was found to accumulate less. The uptake by the tissue was strongly proportional to the extracellular concentration. Atria equilibrated with fentanyl at pH 8.5 released the compound rapidly when exposed to a pH of 7.0, even in the continuous presence of fentanyl in the bath. The consequences of the findings for in vivo conditions are discussed with respect to a possible augmentation of the actions of fentanyl by respiratory acidosis.

Present address: Department of Experimental Medicine Janssen, Raiffeisenstr. 8, 4040 Neuss 21, West-Germany.


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