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Effect of multiple intravenous doses of lanicemine (AZD6765) on the pharmacokinetics of midazolam in healthy subjects

, : Effect of multiple intravenous doses of lanicemine (AZD6765) on the pharmacokinetics of midazolam in healthy subjects. Journal of Clinical Pharmacology 55(9): 1024-1030

The objectives of the present study were to evaluate safety and tolerability as well as the effects of multiple doses of lanicemine on the pharmacokinetics of a CYP3A substrate, midazolam. A total of 46 healthy volunteers were enrolled in the open-label, fixed-sequence, nonrandomized study. All volunteers received an oral dose of 5 mg of midazolam alone or after 6 days of 150 mg daily intravenous infusion of lanicemine. Lanicemine reached a plasma Cmax of 1.51 μg/mL after 150 mg daily dosing to steady state. The geometric mean CL, Vss, and t1/2 of lanicemine were 8.1 L/h, 122.0 L, and 10.4 hours, respectively. The geometric least-squares mean ratios and 90% confidence intervals for midazolam AUC0- ∞ , and Cmax were within the 80% to 125% limits when lanicemine plus midazolam treatment was compared with midazolam alone, demonstrating that daily dosing with 150 mg of lanicemine for 6 days had no effect on CYP3A activity. Comprehensive physiologically based pharmacokinetic modeling using in vitro and in silico findings also indicated lanicemine would have little impact on the pharmacokinetics of CYP3A substrate, such as midazolam. In addition, lanicemine and midazolam administered alone or in combination were generally safe and well tolerated.


PMID: 25880724

DOI: 10.1002/jcph.515

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Rostami, Z.; Hosseini, M.Sadat.; Lessan Pezeshki, M.; Heidari, F.; Einollahi, B., 2014: Bone mineral metabolism and subsequent hospitalization with poor quality of life in dialysis patients. Significant impairment in health-related quality of life (HRQOL) among dialysis patients could be partly explained by some co-morbid disorders, such as chronic kidney disease-mineral and bone disorder (CKD-MBD). Also disturbance in calcium and pho...

Schaich, W.L.; Schider, G.; Krenn, J.R.; Leitner, A.; Aussenegg, F.R.; Puscasu, I.; Monacelli, B.; Boreman, G., 2003: Optical resonances in periodic surface arrays of metallic patches. The transmission of light along the surface normal through an air-quartz-glass interface covered with a periodic array of thin, rectangular gold patches has been studied over the visible to infrared range. The various structures that are observed...

Weichsel, M.E., 1974: Effect of thyroxine on DNA synthesis and thymidine kinase activity during cerebellar development. Brain Research 78(3): 455-465

Jansen, A.J.G.; Caljouw, M.A.A.; Hop, W.C.J.; Van Rhenen, D.J.; Schipperus, M.R., 2002: Feasibility of a restrictive transfusion policy for patients treated with intensive chemotherapy for Acute Myeloid Leukemia. Vox Sanguinis 83(Supplement 2): 133, August

Demestre, M.; Gregson, N.A.; Smith, K.J.; Miller, K.M.; Gearing, A.J.; Hughes, R.A.C., 1999: Effect of a matrix metalloproteinase inhibitor on nerve regeneration. Greenwald, R A [Editor], Zucker, S [Editor], Golub, L M [Editor] Annals of the New York Academy of Sciences; Inhibition of matrix metalloproteinases: Therapeutic applications 658-661

Pond, W.G.; Krook, L.P.; Ho, H.; Su, D.R.; Schoknecht, P.A., 1996: Bone density and tissue lead accretion in growing rats fed low high calcium with or without supplemental clinoptilolite. Bulletin of Environmental Contamination & Toxicology 57(5): 713-721

Ong, Eng Shi, 2002: Chemical assay of glycyrrhizin in medicinal plants by pressurized liquid extraction with capillary zone electrophoresis. Glycyrrhizin in Radix glycyrrhizae or liquorice was determined using a laboratory made dynamic pressurized liquid extraction (PLE) system coupled with capillary zone electrophoresis (CZE). The amount of glycyrrhizin was determined using CZE with a...

Ewquirol; Champagne D.L.briolle A.; Jabiol A.; Massol J D.; Laurent H.; Calvy H., 1969: Radiological aspects following nissens fundo plication. Soc Med Chir Hop Form Sanit Armees Publ Mens 8: 767-771

Dovedova, E.L., 1978: Biochemical characteristics of synaptosomes and mitochondria in the motor cerebral cortex under deprivation of sensory impulsation. Changes in the specific activity of cytochrome oxidase monoamine oxidase, acetylcholinesterase and Na,K-ATPase in the light and heavy synaptosomes and mitochondria of neuron bodies fractions in the motor cerebral cortex of rabbits were demonstrate...

Girard, Maurice., 1867: Note sur l'Aberration Taraxacoides (Bellier dc la Cha vigneric) du Bonibyx castrensis (Linn.). Anuales Soc Ent France 4e seric tome, VI 565-567