caa a22 4500 475818601 CHVBK 20180406123816.0 cr unu---uuuuu 170329e20000701xx s 000 0 eng 10.1007/s002280000146 doi (NATIONALLICENCE)springer-10.1007/s002280000146 Effects of rifampicin and cimetidine on pharmacokinetics and pharmacodynamics of lamotrigine in healthy subjects [Elektronische Daten] [U. Ebert, N. Q. Thong, R. Oertel, W. Kirch] Objective: To study the effects of rifampicin, a potent inducer of the microsomal P 450 enzyme system and of specific isoforms of the uridine 5′-diphosphate(UDP)-glucuronyl-transferase enzyme system, and cimetidine, a known inhibitor of the hepatic microsomal cytochrome P 450 enzyme system, on pharmacokinetics and pharmacodynamics of lamotrigine in healthy subjects. Methods: Ten healthy male subjects received a single oral dose of 25 mg lamotrigine after a 5-day pretreatment with (1) cimetidine 800 mg divided into two equal doses, (2) rifampicin 600 mg, or (3) placebo. Serum and urine samples were analyzed using high-performance liquid chromatography. Changes in electroencephalographic (EEG) power were determined up to 48 h after lamotrigine administration. Results: The values of the pharmacokinetic parameters of lamotrigine were: clearance over bioavailability (CL/F) 2.60 ± 0.40 l/h, renal clearance (CLR) 0.10 ± 0.03 l/h, terminal half-life (t 1/2) 23.8 ± 2.1 h, mean peak serum concentration (Cmax) 0.29 ± 0.02 μg/l, time to reach Cmax (tmax) 1.6 ± 0.28 h, and total area under the serum concentration-time curve (AUC0-∞) 703.99 ± 82.31 μg/ml/min (mean ± SEM). The amount of lamotrigine excreted as glucuronide was 8.90 ± 0.77 mg. Rifampicin significantly increased CL/F (5.13 ± 1.05 l/h) and the amount of lamotrigine excreted as glucuronide (12.12 ± 0.94 mg), whereas both t 1/2 (14.1 ± 1.7 h) and AUC0-∞ (396.24 ± 60.18 μg/ml/min) were decreased (P < 0.05). Cimetidine failed to affect pharmacokinetics of lamotrigine. Lamotrigine did not change EEG power. Conclusion: Rifampicin altered pharmacokinetics of lamotrigine due to induction of the hepatic enzymes responsible for glucuronidation, while coadministration of cimetidine to ongoing lamotrigine therapy has negligible effects on lamotrigine pharmacokinetics. Lamotrigine administered as a single dose of 25 mg has no effect on EEG power in healthy subjects. Springer-Verlag Berlin Heidelberg, 2000 Key words Lamotrigine nationallicence Pharmacokinetics nationallicence Electroencephalogram nationallicence Ebert U. Institute of Clinical Pharmacology, Faculty of Medicine, Technical University Dresden, Fiedlerstrasse 27, D-01307 Dresden, Germany e-mail: uebert@rcs.urz.tu-dresden.de Tel.: +49-351-4582815; Fax: +49-351-4584341, DE aut Thong N. Q. Institute of Clinical Pharmacology, Faculty of Medicine, Technical University Dresden, Fiedlerstrasse 27, D-01307 Dresden, Germany e-mail: uebert@rcs.urz.tu-dresden.de Tel.: +49-351-4582815; Fax: +49-351-4584341, DE aut Oertel R. Institute of Clinical Pharmacology, Faculty of Medicine, Technical University Dresden, Fiedlerstrasse 27, D-01307 Dresden, Germany e-mail: uebert@rcs.urz.tu-dresden.de Tel.: +49-351-4582815; Fax: +49-351-4584341, DE aut Kirch W. Institute of Clinical Pharmacology, Faculty of Medicine, Technical University Dresden, Fiedlerstrasse 27, D-01307 Dresden, Germany e-mail: uebert@rcs.urz.tu-dresden.de Tel.: +49-351-4582815; Fax: +49-351-4584341, DE aut https://doi.org/10.1007/s002280000146 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280000146 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ebert U. Institute of Clinical Pharmacology, Faculty of Medicine, Technical University Dresden, Fiedlerstrasse 27, D-01307 Dresden, Germany e-mail: uebert@rcs.urz.tu-dresden.de Tel.: +49-351-4582815; Fax: +49-351-4584341, DE aut NATIONALLICENCE 700 1- Thong N. Q. Institute of Clinical Pharmacology, Faculty of Medicine, Technical University Dresden, Fiedlerstrasse 27, D-01307 Dresden, Germany e-mail: uebert@rcs.urz.tu-dresden.de Tel.: +49-351-4582815; Fax: +49-351-4584341, DE aut NATIONALLICENCE 700 1- Oertel R. Institute of Clinical Pharmacology, Faculty of Medicine, Technical University Dresden, Fiedlerstrasse 27, D-01307 Dresden, Germany e-mail: uebert@rcs.urz.tu-dresden.de Tel.: +49-351-4582815; Fax: +49-351-4584341, DE aut NATIONALLICENCE 700 1- Kirch W. Institute of Clinical Pharmacology, Faculty of Medicine, Technical University Dresden, Fiedlerstrasse 27, D-01307 Dresden, Germany e-mail: uebert@rcs.urz.tu-dresden.de Tel.: +49-351-4582815; Fax: +49-351-4584341, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer