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Effect of simultaneous treatment with low doses of perphenazine on plasma and urine concentrations of nortriptyline and 10-hydroxynortriptyline

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Plasma levels of nortriptyline and perphenazine were measured in six patients on continuous nortriptyline treatment before, during and after oral administration of perphenazine 4 mg t.i.d. In four patients the plasma levels of the conjugated and unconjugated principal metabolite 10-hydroxy-nortriptyline were also measured. Urinary excretion of conjugated and unconjugated 10-hydroxy-nortriptyline and plasma levels of perphenazine were determined in all six patients. During treatment with perphenazine two patients showed a slight increase in the plasma level of nortriptyline. The changes in metabolite excretion rate were inconclusive. Thus, there did not appear to be any important pharmacokinetic interaction between the two drugs at the doses used, which were normal therapeutic doses. The previously reported inhibitory effect of perphenazine on the metabolism of nortriptyline probably depended therefore, either on administration of a higher dose of perphenazine, or on treatment in the reverse sequence — a single dose of nortriptyline was given to patients already receiving perphenazine.

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  • Alexanderson, B., Borgå, O.: Urinary excretion of nortriptyline and five of its metabolites in man after single and multiple oral doses. Europ. J. clin. Pharmacol.5, 174–180 (1973)

    Google Scholar 

  • von Bahr, C.: Binding and oxidation of amitriptyline and a series of its oxidized metabolites in liver microsomes from untreated and phenobarbital treated rats. Xenobiotica2, 293–306 (1972)

    Google Scholar 

  • Borgå, O., Palmér, L., Sjöqvist, F., Holmstedt, B.: Mass fragmentography used in quantitative analysis of drugs and endogenous compounds in biological fluids. In: Symposium on the Basis of Drug Therapy in Man. Fifth Internat. Pharmacol. Congr., San Francisco, July 1972. Vol 3. C/9. pp 56–68 (1973)

  • Hammer, W., Sjöqvist, F.: Inhibition of the metabolism of tremorine and oxotremorine in rats by antidepressants of the imipramine-type. In: Proc. First Internat. Symposium on Antidepressant Drugs. Milan, 1966, Ed. S. Garattini and M.N.G. Dukes: Excerpta Med.Internat. Congr. Ser. No. 122, 279–289. Amsterdam: Excerpta Medica 1967

    Google Scholar 

  • Hansen, C.E., Larsen, N.E.: Perphenazine concentrations in human whole blood. Psychopharmacologia37, 31–36 (1974)

    Google Scholar 

  • Hansen, C.E., Christensen, T.R., Elley, J., Hansen, L.B., Kragh-Sørensen, P., Larsen, N.-E., Næstoft, J., Hvidberg, E.F.: Clinical pharmacokinetic studies of perphenazine. Brit. J. clin. Pharmacol.3, 915–923 (1976)

    Google Scholar 

  • Gram, L.F., Fredricson-Overø, K.: Drug interaction: Inhibitory effects of the neuroleptics on metabolism of tricyclic antidepressants in man. Brit. Med. J.1972 I, 463–465

    Google Scholar 

  • Gram, L.F., Fredricson-Overø, K., Kirk, L.: Influence of neuroleptics and benzodiazepines on metabolism of tricyclic antidepressants in man. Amer. J. Psychiatry131:8, 863–866 (1974a)

    Google Scholar 

  • Gram, L.F., Christiansen, J., Fredricson-Overø, K.: Pharmacokinetic interaction between neuroleptics and tricyclic antidepressants in the rat. Acta Pharmacol. Toxicol.35, 223–232 (1974b)

    Google Scholar 

  • Gram, L.F.: Effects of perphenazine on imipramine metabolism in man. Psychopharmacol. Comm.1, 165–175 (1975)

    Google Scholar 

  • Kragh-Sørensen, P., Hansen, C.E., Asberg, M.: Plasmanortriptyline levels in endogenous depression. Lancet1973 I, 113–115

    Google Scholar 

  • Kragh-Sørensen, P., Hansen, C.E., Baastrup, P.C., Hvidberg, E.: Self-inhibiting action of nortriptylines antidepressive effect at high plasma levels. Psychopharmacology45, 305–312 (1976)

    Google Scholar 

  • Larsen, N.E., Næstoft, J.: Determination of perphenazine and fluphenazine in whole blood by gas chromatography. Med. Lab. Technol.30, 129–132 (1973)

    Google Scholar 

  • Moody, A., Tait, C., Todrick, A.: Plasma levels of imipramine and desmethylimipramine during therapy. Brit. J. Psychiatry113, 183–193 (1967)

    Google Scholar 

  • Olivier-Martin, R., Marzin, D., Buschsen-Schutz, E., Pichot, P., Boissier, J.: Concentrations plasmatiques de l'imipramine et de la desmethyl-imipramine et effect anti-depresseur au cours d'en traitement controlé. Psychopharmacologia41, 187–195 (1975)

    Google Scholar 

  • Sjöqvist, F., Hammer, W., Schumacher, H., Gillette, J.R.: The effect of desmethylimipramine and other “anti-tremorine” drugs on the metabolism of tremorine and oxotremorine in rats and mice. Biochem. Pharmacol.17, 915–934 (1968)

    Google Scholar 

  • Sjöqvist, F.: Assessment of antidepressants — Pharmacokinetic aspects. In: Advanced Medicine Symposia: Topics in Therapeutics, (Ed. A. Breckenridge) pp 198–217. London: Pitman Medical 1975

    Google Scholar 

  • Stevenson, I.H., Schiff, A.A.: The effect of fluphenazineon steady-state plasma levels of nortriptyline. Brit. J. Clin. Pharmacol.1, 337–338 (1974)

    Google Scholar 

  • Åsberg, M., Cronholm, B., Sjöqvist, F., Tuck, D.: Relationship between plasma levels and therapeutic effect of nortriptyline. Brit. Med. J.1971 III, 331–334

    Google Scholar 

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Kragh-Sørensen, P., Borgå, O., Garle, M. et al. Effect of simultaneous treatment with low doses of perphenazine on plasma and urine concentrations of nortriptyline and 10-hydroxynortriptyline. Eur J Clin Pharmacol 11, 479–483 (1977).

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