The effect of parenteral imipramine on the oral absorption of lamotrigine in rats |
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| Affiliation: | 1. Dpt. of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czechia;2. Dpt. of Neurology, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czechia;3. Value Outcomes s.r.o., Prague, Czechia;4. Dpt of Neurology, KZ a.s., Hospital Teplice, Teplice, Czechia;5. Clinic of Neurology, University Hospital Ostrava, Ostrava, Czechia;6. Dpt. of Neurology, Charles University in Prague, Faculty of Medicine and University Hospital Hradec Kralove, Hradec Kralove, Czechia;7. Dpt. of Neurology, Charles University in Prague, Faculty of Medicine in Pilsen and University Hospital Pilsen, Pilsen, Czechia;8. Neurology Clinic, Pardubice Regional Hospital and Faculty of Health Studies, University of Pardubice, Pardubice, Czechia;9. Dpt. of Neurology, Hospital of Jihlava, Jihlava, Czechia;10. Dpt. of Neurology, Thomayer Hospital, Prague, Czechia;11. Charles University in Prague, Third Faculty of Medicine, Charles University and Hospital Kralovske Vinohrady, Prague, Czechia;12. Dpt. of Neurology, University Hospital and Masaryk University, Brno, Czechia;13. Dpt. of Neurology, Faculty of Medicine, Palacky University and University Hospital Olomouc, Olomouc, Czechia;14. First Dpt. of Neurology, Masaryk University, St. Anne''s University Hospital, Brno, Czechia;15. Dpt. of Neurology, Tomas Bata Regional Hospital, Zlin, Czechia;p. Dpt. od Neurology, Hospital Ceske Budejovice, Ceske Budejovice, Czechia;q. Dpt. of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Czechia;1. Arkansas Epilepsy Program, #2 Lile Court Suite 100, Little Rock, AR 72205, USA;2. Department of Neurology, Epilepsy Program, Hospital Ruber Internacional, La Masó 38, 28034 Madrid, Spain;3. UCB Pharma, 8010 Arco Corporate Drive, Raleigh, NC 27617, USA;4. FE Dreifuss Comprehensive Epilepsy Program, University of Virginia, Box 800394, Charlottesville, VA 22908, USA;2. Division of Clinical Data Analytics and Decision Support, University of Arizona College of Medicine—Phoenix, Phoenix, AZ, United States;3. Division of Medical Toxicology and Precision Medicine, University of Arizona College of Medicine—Phoenix, Phoenix, AZ, United States;1. Cornwall Partnership NHS Foundation Trust, Chygovenck, Three milestone Industrial Estate, Truro, TR4 9LD, Cornwall, UK;2. Royal Cornwall Hospital Trust, , Truro, TR1 3LQ, Cornwall, UK;3. Exeter Medical School Knowledge Spa, TR1 3LQ, Cornwall, UK |
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| Abstract: | ![]()
The interaction between imipramine and lamotrigine was investigated following the acute administration of lamotrigine (20 mg kg−1, p.o.) alone or together with imipramine (25 mg kg−1, i.p.) to rats. Similarly, the same doses of lamotrigine alone or when they were given together with imipramine (15 mg kg−1, i.p.) were administered to rats chronically for 5 days. Plasma samples were collected at 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0 and 24.0 h after lamotrigine administration. An assay of lamotrigine in plasma was performed using a high-performance liquid chromatographic (HPLC) method. The concomitant administration of imipramine (25 mg kg−1, i.p) with lamotrigine (20 mg kg−1, p.o.) acutely, resulted in a significant (P<0.05) decrease in the maximum plasma concentration (Cmax), the mean area under the plasma concentration–time curve (AUC) and the half-life (t1/2), and a significant decrease (P<0.001) in the time to reach maximum concentration (tmax), as compared to those obtained for lamotrigine alone. Similarly, the chronic administration of imipramine together with lamotrigine lead to significant decreases in Cmax, AUC and t1/2 while the tmax remained unchanged. These results suggest that a significant decrease in the absorption of lamotrigine occurs when it is given acutely or chronically together with the antidepressant imipramine. |
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