caa a22 4500 475818814 CHVBK 20180406123816.0 cr unu---uuuuu 170329e20001101xx s 000 0 eng 10.1007/s002280000192 doi (NATIONALLICENCE)springer-10.1007/s002280000192 Ciprofloxacin increases serum clozapine and N -desmethylclozapine: a study in patients with schizophrenia [Elektronische Daten] [K. Raaska, P.J. Neuvonen] Abstract.: Objective: A possible pharmacokinetic interaction between a CYP1A2 inhibitor, ciprofloxacin, and clozapine was studied in schizophrenia patients with stable clozapine treatment. Methods: A randomised double-blind cross-over study design with two phases was used. Seven schizophrenic inpatients volunteered to receive, in addition to their previous drug regimen, either 250mg ciprofloxacin or placebo twice daily (b.i.d.) for 7days. The phases were separated by a 7-day wash-out period. Serum concentrations of clozapine and its main metabolite N-desmethylclozapine were measured during both phases before the first dose on day1 and on days3 and 8. Results: Ciprofloxacin increased mean serum concentration of clozapine and N-desmethylclozapine by 29% (P<0.01) and 31% (P<0.05), respectively. There was a significant positive correlation (r=0.90, P<0.01) between the individual concentrations of serum ciprofloxacin and the increase in concentrations of clozapine plus N-desmethylclozapine. The increase in serum clozapine concentrations correlated significantly (r=0.89, P<0.01) with the ratios of N-desmethylclozapine to clozapine concentrations. Conclusion: Even a low dose of ciprofloxacin can moderately increase serum concentrations of clozapine and N-desmethylclozapine. A probable mechanism of interaction is an inhibition of CYP1A2 enzyme by ciprofloxacin. The possibility of clinically significant interaction should be considered, especially when higher doses of ciprofloxacin are used concomitantly with clozapine. Springer-Verlag, 2000 Clozapine Ciprofloxacin CYP1A2 nationallicence Raaska K. Department of Psychiatry, University of Helsinki and Kellokoski Hospital, Finland aut Neuvonen P.J. Department of Clinical Pharmacology, University of Helsinki, Haartmaninkatu 4, FIN-00290, Helsinki, Finland aut European Journal of Clinical Pharmacology Springer-Verlag 56/8(2000-11-01), 585-589 0031-6970 56:8<585 2000 56 228 https://doi.org/10.1007/s002280000192 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000192 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Raaska K. Department of Psychiatry, University of Helsinki and Kellokoski Hospital, Finland aut NATIONALLICENCE 700 1- Neuvonen P.J. Department of Clinical Pharmacology, University of Helsinki, Haartmaninkatu 4, FIN-00290, Helsinki, Finland aut NATIONALLICENCE 773 0- European Journal of Clinical Pharmacology Springer-Verlag 56/8(2000-11-01), 585-589 0031-6970 56:8<585 2000 56 228 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer