In patients with liver or kidney disease, it is especially important to consider the routes of metabolism and elimination of small-molecule pharmaceuticals. Once in the blood, numerous drugs are taken up by the liver for metabolism and/or biliary elimination, or by the kidney for renal elimination. Many common drugs are organic anions. The major liver uptake transporters for organic anion drugs are organic anion transporter polypeptides (OATP1B1 or SLCO1B1; OATP1B3 or SLCO1B3), whereas in the kidney they are organic anion transporters (OAT1 or SLC22A6; OAT3 or SLC22A8). Since these particular OATPs are overwhelmingly found in the liver but not the kidney, and these OATs are overwhelmingly found in the kidney but not liver, it is possible to use chemoinformatics, machine learning (ML) and deep learning to analyze liver OATP-transported drugs versus kidney OAT-transported drugs. Our analysis of >30 quantitative physicochemical properties of OATP- and OAT-interacting drugs revealed eight properties that in combination, indicate a high propensity for interaction with “liver” transporters versus “kidney” ones based on machine learning (e.g., random forest, k-nearest neighbors) and deep-learning classification algorithms. Liver OATPs preferred drugs with greater hydrophobicity, higher complexity, and more ringed structures whereas kidney OATs preferred more polar drugs with more carboxyl groups. The results provide a strong molecular basis for tissue-specific targeting strategies, understanding drug–drug interactions as well as drug–metabolite interactions, and suggest a strategy for how drugs with comparable efficacy might be chosen in chronic liver or kidney disease (CKD) to minimize toxicity.

Ketamine has recently been shown to be non-inferior to electroconvulsive therapy (ECT), one of psychiatry’s most effective treatments for depression. Given the novelty of ketamine as well as its interventional nature, ketamine is currently viewed as an alternative to ECT and as such, considered a third-line agent for treatment-refractory depression. However, available data suggest that ketamine carries a low side-effect burden and is better tolerated than many second-line augmentation strategies for depression. With this combination of higher efficacy and lower side-effect burden in conjunction with what is known about treatment outcomes in relation to the duration of untreated illness, it is in the best interest of patients for the field of psychiatry to evaluate ketamine as a second-line augmentation strategy for refractory depression.

Evidence indicates that ketamine is highly effective, has a lower side effect profile and is better tolerated compared to many augmentation strategies for refractory depression. This, combined with data on psychiatric treatment outcome mediators, suggests that earlier intervention with ketamine could improve outcomes for patients suffering from refractory depression.