Selective serotonin reuptake inhibitors and theophylline metabolism in human liver microsomes: potent inhibition by fluvoxamine.

• DOI: 10.1111/j.1365-2125.1995.tb04422.x
• Publication Date: 2012-07-05T04:34:13Z
• Authors: BB Rasmussen; J Maenpaa; O Pelkonen; S Loft; HE Poulsen; J Lykkesfeldt; K Brosen
• Keywords: Fluvoxamine; Chlorzoxazone; Sertraline; Unspecific monooxygenase

1. Fluvoxamine and seven other selective serotonin reuptake inhibitors (SRRI) were tested for their ability to inhibit a number of human cytochrome P450 isoforms (CYPs). 2. None the drugs showed potent inhibition CYP2A6 (coumarin 7‐hydroxylase) or CYP2E1 (chlorzoxazone 6‐hydroxylase), while norfluoxetine was only inhibitor CYP3A having IC50 values 11 microM 19 testosterone 6 beta‐hydroxylase cortisol beta‐hydroxylase, respectively. 3. Norfluoxetine, sertraline fluvoxamine inhibited CYP1A1 (7‐ ethoxyresorufin O‐deethylase) in microsomes from placenta (IC50 29 microM, 35 80 respectively). CYP1A2‐mediated 7‐ethoxyresorufin O‐ deethylase activity = 0.3 microM) liver. 4. In three livers potently all pathways theophylline biotransformation, apparent constant, Ki, 0.07‐0.13 0.05‐0.10 0.16‐0.29 1‐methylxanthine, 3‐methylxanthine 1,3‐ dimethyluric acid formation, Seven SSRIs either weak no metabolism. 5. Ethanol formation 1,3‐dimethyluric with K(i) value 300 which is consistent CYP2E1. both 8‐hydroxylation by about 45% and, combination, compounds decreased 90%, indicating that CYP1A2 are equally important theophylline. 6. It concluded pharmacokinetic interaction between due CYP1A2.