Hyperkalemia is a potentially life-threatening condition, and patients who have chronic kidney disease, who are diabetic, or who are taking renin–angiotensin–aldosterone system inhibitors are at increased risk. Therapeutic options for hyperkalemia tend to have limited effectiveness and can be associated with serious side effects. Colonic potassium secretion can increase to compensate when urinary potassium excretion decreases in patients with renal impairment, but this adaptation is insufficient and hyperkalemia still results. Patiromer is a novel, spherical, nonabsorbed polymer designed to bind and remove potassium, primarily in the colon, thereby decreasing serum potassium in patients with hyperkalemia. Patiromer has been found to decrease serum potassium in patients with hyperkalemia having chronic kidney disease who were on renin–angiotensin–aldosterone system inhibitors. Results of nonclinical studies and an early phase clinical study are reported here. Two studies with radiolabeled drug, one in rats and the other in dogs, confirmed that patiromer was not absorbed into the systemic circulation. Results of an in vitro study showed that patiromer was able to bind 8.5 to 8.8 mEq of potassium per gram of polymer at a pH similar to that found in the colon and had a much higher potassium-binding capacity compared with other resins, including polystyrene sulfonate. In a study in hyperkalemic rats, a decrease in serum potassium was observed via an increase in fecal potassium excretion. In a clinical study in healthy adult volunteers, a significant increase in fecal potassium excretion and a significant decrease in urinary potassium excretion were observed. Overall, patiromer is a high-capacity potassium binder, and the chemical and physical characteristics of patiromer may lead to good clinical efficacy, tolerability, and patient acceptance.

An electrochemical approach to assessing the degree of electronic coupling in mixed-valence binuclear complexes is outlined. The method relies on the comparison of electrochemical potential shifts induced at both the directly and indirectly perturbed metal sites when a ligand substitution process is carried out at one site, e.g., [symmetric] ( N H~)~R U -L~~R U ( N H~)~~+ /~+ /~+ -[asymmetric] L(NH~)~RU-LI,,-R~(NH~)~~+/~+/~+, where the bridging ligandLbr is either pyrazine or 4-cyanopyridine and the perturbing ligand L is a substituted pyridine. It is found that the degree of electronic coupling in these systems is at least three times that which would be predicted based solely on spectroscopic measurements. The stabilization energy due to electron delocalization in these complexes can be accounted for with near-quantitative accuracy. It is also shown how the Mulliken analysis of the data allows for an estimation of the Wolfsberg-Helmholz constant K, which can be used in the calculation of off-diagonal matrix elements for molecular donor-acceptor interactions. (6) De la Rosa, R.; Chang, P. J.; Salaymeh, F.; Curtis, J. C. Inorg. Chem. 1985,24,4229-423 1. (7) Theuseofsubstitutbdpyridinesto'tune"thegroundandexcitcd electronic propcrticsof ruthenium amminecomplexes has been extensively employed by Ford and co-workers: (a) Malouf, G.; Ford, P. C.

4229The results presented here provide not only a synthetic method of a new type of chromium(II1) porphyrin complex but also an insight into the axial coordination mode of Cr(II1)-substituted cytochrome P450 if it is prepared.Acknowledgment. Redox Asymmetry and Metal-Metal Coupling in Pyrazine-Bridged Ruthenium Dimers Sir:Elucidation of the nature and extent of electronic coupling in mixed-valenck dimers continues to present a challenging theoretical and experimental problem.'-' The pyrazine-bridged diruthenium decaammine species [ R~( N H~)~l~p y z~+ (the Creutz-Taube ion4) presents a particularly intriguing case since it does not appear to fall squarely into either the predominantly valence-localized Robin and Day class I1 category or the fully delocalized class I11 category.s-6Brown, D. M., Ed. 'Mixed-Valence Compounds"; D. Reidel: Dordrecht, Holland, 1980.

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