Rencofilstat (RCF) is a novel cyclophilin inhibitor under development for the treatment of nonalcoholic steatohepatitis and hepatocellular carcinoma. This phase 1, randomized, open-label study in healthy participants assessed the relative bioavailability of a single dose of RCF 225-mg soft gelatin capsules in both fasted and high-fat conditions. Forty-four participants were enrolled to either the fasted (n = 24) or the high-fat fed (n = 20) arm. Noncompartmental pharmacokinetics were evaluated following a single 225-mg oral dose. Administration of RCF with a high-fat meal led to increases in maximum concentration, area under the concentration-time curve (AUC) from time 0 to 24 hours, and AUC from time 0 to infinity fed-to-fasted geometric mean ratios of 102.2%, 114.5%, and 132.9%, respectively. All AUC geometric mean ratios were outside of the 80% to 125% range, suggesting that a high-fat meal can increase the extent of RCF exposure. Time to maximum concentration increased from 1.5 to 1.8 hours in the fasted and high-fat groups, respectively, suggesting slightly delayed absorption. High fat intake may delay gastric emptying while increasing the absorption and bioavailability of RCF. No treatment-emergent adverse events were observed in the fasted group, and 1 treatment-emergent adverse event occurred in the high-fat meal group. The differences in observed whole-blood concentrations are unlikely to have clinically relevant effects given the wide therapeutic index of RCF demonstrated in previous phase 1 studies.

According to the World Health Organization (WHO), the worldwide prevalence of smoking tobacco among males remains over 40%; therefore, physicians should continue to strive to motivate patients to quit smoking using new and old techniques. Most smokers in developed countries know smoking has negative health effects, and nearly half try to quit each year. A dose-response relationship exists between smoking cessation counseling and its effectiveness. The mnemonic "STAR" outlines the essential steps for smoking cessation: help patients set a quit date; tell family and friends and ask for social support; anticipate and plan for challenges in quitting smoking, including withdrawal; and remove all tobacco products. Patients should develop an individual plan of action to address challenges in quitting. A motivational intervention may promote smoking cessation in smokers who state they are not ready to quit. Minimizing withdrawal symptoms with pharmacotherapy is very helpful. The new Food and Drug Administration-approved medication Chantix results in higher quit rates than bupropion in published studies. This article concludes with a discussion of the effectiveness of alternative therapies and a handout for patients.

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