Abstract
Twelve healthy male volunteers took part in a double-blind randomised cross-over study composed of three treatment sessions: remoxipride 100 mg; remoxipride 100 mg plus biperiden 4 mg; and biperiden 4 mg. Plasma and urine concentrations of remoxipride and biperiden, plasma prolactin levels, salivary flow and adverse events were recorded to assess pharmacodynamic interactions. Remoxipride and biperiden had no effect on each other's plasma concentrations. Biperiden did not affect the urinary recovery or renal clearance of remoxipride. Prolactin levels were unaffected by biperiden but increased following remoxipride administration. Differences in prolactin Cmax and tmax following remoxipride versus concomitant (remoxipride + biperiden) treatment were not statistically significant. However, a slight but statistically significant (P=0.04) increase in prolactin AUC was observed after concomitant treatment. No significant differences could be observed between the recorded salivary flow in all the treatment sessions. Single doses of remoxipride and biperiden showed no pharmacokinetic or pharmacodynamic interaction.
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References
Bamrah JS, Kumar J, Krska J, Soni SD (1986) Interactions between procyclidine and neuroleptic drugs. Some pharmacological and clinical aspects. Br J Psychiatry 149:726–733
Bahr C von, Movin G, Yisak W-A, Jostell K-G, Widman M (1990) Clinical pharmacokinetics of remoxipride. Acta Psychiatr Scand 82 [Suppl 358]:41–44
Conti L, Andreani MF, Bonollo L, Martini A (1984) Iatrogenic parkinsonism: the efficacy of treatment with biperiden. Curr Ther Res 36:217–227
Farde L, Grind M, Nilsson M-I, Ogenstad S, Sedvall G (1988) Remoxipride — a new potential antipsychotic drug. Pharmacological effects and pharmacokinetics following repeated oral administration in male volunteers. Psychopharmacology 95:157–161
Fredriksson G (1988a) Determination of biperiden in human plasma by gas chromatography-mass fragmentography. Astra Method 805–17 AFB 10, 1988-07-07
Fredriksson G (1988b) Determination of biperiden in human urine by gas chromatography-mass fragmentography. Astra Method 805–17 AFB 11, 1988-07-07
Friis T, Christensen R, Gerlach J (1983) Sodium valproate and biperiden in neuroleptic-induced parkinsonism and hyperkinesia. Acta Psychiatr Scand 67:178–187
Gautier J, Jus A, Villeneuve A, Jus K, Pires P, Villeneuve R (1977) Influence of antiparkinsonian drugs on the plasma levels of neuroleptics. Biol Psychiatry 12:389–399
Gibaldi M, Perrier D (1982) Pharmacokinetics. Marcel Dekker, New York
Grimaldi R, Perruca E, Ruberto G, Gelmi C, Trimarchi F, Hollman M, Crema A (1986) Pharmacokinetic and pharmacodynamic studies following the intravenous and oral administration of the antiparkinsonian drug biperiden to normal subjects. Eur J Clin Pharmacol 29:735–737
Halbreich U, Sachar EJ, Nathan RS, Asnis GM, Halpern FS (1980) The effect of benztropine on the prolactin response to haloperidol. Psychopharmacology 72:61–65
Hansen LB, Elley J, Christensen TR, Larson NE, Naestoft J, Hvidberg EF (1979) Plasma levels of perphenazine and its major metabolites during simultaneous treatment with anticholinergic drugs. Br J Clin Pharmacol 7:75–80
Hollander M, Wolfe DA (1973) Non parametric statistical methods. Wiley, New York
Hollman M, Brode E, Greger G, Müller-Peltzer H, Wetzelberger N (1984) Biperiden effects and plasma levels in volunteers. Eur J Clin Pharmacol 27:619–621
Janowsky DS, Risch SC, Judd LL, Huey LY, Parker DC (1985) Basic cholinergic systems and the pathogenesis of affective disorders. In: Singh MM, Warburton DM, Lal H (eds) Central cholinergic mechanism and adaptive dysfunction. Plenum Press, New York, pp 309–353
Johnstone EC, Crow TJ, Ferrier IN, Frith CD, Owens DGC, Bourne RD, Gamble SJ (1983) Adverse effects of anticholinergic medication on positive schizophrenic symptoms. Psychol Med 13:513–527
Jostell K-G, Lapierre YD, and the Canadian study group (1990) Plasma concentration of remoxipride in relation to antipsychotic effect and adverse symptoms. Acta Psychiatr Scand 82 [Suppl 358]:48–50
Lal S, Mendis T, Cervantes P, Guyda H, de Rivera JL (1979) Effects of benztropine on haloperidol induced prolactin secretion. Neuropsychobiology 5:327–331
Lewander T, Westerbergh S-E, Morrison D (1990) Clinical profile of remoxipride- a combined analysis of a comparative double-blind multicentre trial programme. Acta Psychiatr Scand 82 [Suppl 358]:92–98
Linnoila M, Viukari M, Vaisanen (1980) Effects of anticonvulsant drugs on plasma haloperidol and thioridazine levels. Am J Psychiatry 137:819–821
Loga S, Curry S, Lader M (1975) Interactions of orphenadrine and phenobarbitone with chlorpromazine. Plasma concentrations and effects in man. Br J Clin Pharmacol 2:197–208
McEvoy JP (1983) The clinical use of anticholinergic drugs as treatment for extrapyramidal side effects of neuroleptic drugs. J Clin Psychopharmacol 3:288–302
Morselli PL, Zarifian E, Cuche H, Bianchetti G, Cotterau MJ, Deniker P (1980) Haloperidol plasma levels monitoring in psychiatric patients. In: Cattabeni P et al (eds) Long term effect of neuroleptics. Raven Press, New York, pp 529–536
Nathan RS, Perel JM, McCarthy T, Barret DB (1985) Effect of benztropine on the diurnal prolactin responses to haloperidol. Psychoneuroendocrinology 10:71–76
Nilsson L (1990) Determination of remoxipride in plasma and urine by reversed phase column liquid chromatography. J Chromatogr 526:139–150
Ögren SO, Hall H, Köhler C, Magnusson O, Lindbom LO, Ängeby K, Florvall L (1984) Remoxipride, a new potential antipsychotic compound with selective antidopaminergic action in the rat brain. Eur J Pharmacol 102:459–474
De Rivera JL, Lal S, Ettigi P, Hontela S, Muller HF, Friesen HG (1976) Effect of acute and chronic neuroleptic therapy on serum levels in men and women of different age groups. Clin Endocrinol 5:273–282
Rivera-Calimlim L, Nasrallah H, Strauss J, Lasagna L (1976) Clinical response and plasma levels: effect of dose and drug interactions on plasma chlorpromazine levels. Am J Psychiatry 133:646–652
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Yisak, W., Farde, L., von Bahr, C. et al. Interaction study between remoxipride and biperiden. Psychopharmacology 111, 27–32 (1993). https://doi.org/10.1007/BF02257403
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DOI: https://doi.org/10.1007/BF02257403