HPLC with Fluorometric Detection of Brain Catecholamines in a Pharmacodynamic Study Between Two Popular Antidepressants

Abstract

Drug-drug interactions are a serious concern in US health care today, accounting for over 100,000 deaths annually. Bupropion (Wellbutrin®) is a well-established monocyclic antidepressant that is also used in the treatment of smoking cessation. Sertraline (Zoloft®) is a commonly prescribed 28 selective serotonin re-uptake inhibitor (SSRI), and is used in the treatment of depression and other mood anxiety disorders. Interestingly, bupropion and sertraline are often co-prescribed in mentally ill patients, yet the danger and clinical consequences of a potential drug-drug interaction between these drugs is poorly studied. Recent studies indicate that sertraline is a potent in vitro inhibitor of bupropion clearance, suggesting potential in vivo pharmacokinetic (PK) and pharmacodynamic (PD) consequences following their co-administration. The aim of this study was to evaluate bupropion brain PD following repeated administration of sertraline in male CF-1 mice. An automated highpressure liquid chromatography (HPLC) system coupled to a fluorescence detector was used to determine whole brain concentrations of three major catecholamines: norepinephrine (NE), dopamine (DA) and serotonin (5-HT). The retention times for NE, DA, isoproterenol (IS) and 5HT were 6.0 min, 13.0 min, 22.0 min and 33.0 min respectively. Following 6 days repeated treatment of either vehicle control or sertraline 15 mg/kg, mice were administered single dose bupropion 50 mg/kg. At 60 min post-dose whole brain tissues were isolated and later analyzed by HPLC. Our results demonstrate that there were no statistical differences in any brain catecholamine levels between bupropion and bupropion plus sertraline treated mice.