Modulation in Pharmacokinetic Properties of Mirtazapine and Citalopram During Contemporaneous Therapy with Ritonavir

摘要

The present study was carried out to evaluate the drug-drug interaction between antidepressant and antiretroviral drugs. Interaction of Mirtazapine, the known antidepressant drug and citalopram, the known SSRI class antidepressant drug with Ritonavir, the known protease Inhibitor antiretroviral drug was evaluated in Mice. In silico (Molecular modeling) studies on interaction of Ritonavir with the mirtazapine and citalopram was done by biosuite version 3.0 (TATA consultancy service limited), where as in vivo studies were done by following forced swim test and compulsive gnawing test. In silico study (Molecular modeling study) shows that ritonavir is having more binding affinity towards CYP2D6 compare to mirtazapine and citalopram, which indicate that Ritonavir may inhibit the metabolism of mirtazapine and citalopram. In vivo study result indicate that Ritonavir (100 mg kg(-1), p.o.) pretreatment has not significantly altered the onset of antidepressant effect of Mirtazapine (10 mg kg(-1), p.o.) but significantly increased the peak antidepressant effect in mice (19.97+-0.4906% antidepressant activity before treatment to 23.99+-0.4162% antidepressant activity after treatment), while duration of antidepressant effect was increased from 18 h to more than 20 h in both groups. Similarly pretreatment with Ritonavir (100 mg kg(-1), p.o.) has significantly no effect on the onset of antidepressant effect of Citalopram (5 mg kg(-1), p.o.) but it significantly increased the peak antidepressant effect in mice (34.16+-1.348% reduction before treatment to 36.66+-0.9426% reduction after treatment), while duration of antidepressant effect was increased significantly to the more than 24 h. This study indicates that Therapeutic Drug Monitoring (TDM) has to be required to readjust the therapeutic doses of Ritonavir and antidepressant drugs like Mirtazapine and Citalopram when they used concomitantly.