*3.2. Lonafarnib*

Lonafarnib (LNF) is a farnesyl transferase inhibitor, which blocks assembly and secretion of virions in the cell (IC50: 36 nM) through the hepatitis delta antigen prenylation [15,26]. LNF has dose and time-dependent pharmacokinetics with an insignificant renal excretion [27]. Moreover, this drug notoriously has some adverse events, mostly in the multiple-dose rather than once-daily administration, mainly reported as minor gastrointestinal disorders, which significantly decreased with food intake [28]. Although the recommended dose is 200 mg bid [29], a recent PK and PD study showed that a high LNF dose of 610 mg bid would achieve 99% efficacy. However, such a high dose might cause several adverse effects [30]. Therefore, the authors provided an already explored suggestion regarding the use of a ritonavir booster to potentially optimize both the LNF tolerability and its antiviral effect [31]. The true ramifications of this option will need to be extensively investigated. Finally, the work of Lempp and colleagues indicates that, besides the suppression of viral secretion, LFN led to an intracellular accumulation of a hepatitis delta antigen [26].
