Crystalline Diseases
In the U.S., probenecid is the only available uricosuric and allopurinol is the only xanthine oxidase inhibitor. There are few therapeutic options available for patients who do not tolerate these drugs. The following 2 abstracts describe promising new agents which hopefully will be made available to U.S. patients.
Abstract # 1289 Efficacy of Uricosuric Therapy in Renal Transplant Patients F Perez-Ruiz, M Calabozo, E Ruiz-Lucea, J Duruelo, A Herrero-Beites, A Alonso, P Gomez-Ullate. Spain.
The benzofuran uricosurics, such as benziodarone, are agents that are available in Europe, South Africa and Japan. Hyperuricemia is a common problem in renal transplant patients. This study demonstrates that in a group of hyperuricemic renal transplant patients, benziodarone was tolerated and effective in increasing excretion of urate and in decreasing serum uric acid. Proper control of uricemia may be achieved with benzofuran uricosurics in patients on cyclosporin, but low dosed (under 75 mg/day) may be insufficient, especially in patients on diuretic therapy or patients with lower renal function. Use of this agent also avoids allopurinol-azathioprine interactions.
Abstract # 2009 Dose-Related Decreases in Uric Acid Observed in a Multiple-Dose Safety, Pharmacokinetic, and Pharmacodynamic Study of TMX-67, A Novel Xanthine Oxidase/Dehydrogenase Inhibitor, in Healthy Subjects R Khosravan, B Bopp, M Cox, R Dean, R Wilson, I Weston. Illinois and Arizona.
TMX-67 is a novel, xanthine oxidase/dehydrogenase inhibitor being developed for the treatment of hyperuricemia associated with gout. Xanthine oxidase/dehydrogenase is the enzyme involved in metabolism of xanthine to uric acid. The data in this study indicate that TMX-67 is very well tolerated and effectively decreases serum uric acid levels in normal subjects within the dosage range studied in this ongoing clinical trial. These results suggest that TMX-67 has potential to be a useful urate-lowering agent in the management of gout.
Abstract # 2010 Dissolution of Calcium Pyrophosphate Crystals by Polyphosphates M Catenaccio, D Chindamo, S Lorenzini, E Selvi S Cucini, R Marcolongo. Italy.
The purpose of this study was to determine the dissolving ability (DA) of linear tripolyphosphate sodium salt (PSTP), cyclic trimetaphosphate sodium salt (TMSP), polymeric metaphosphate sodium salt (SMP) on synthetic crystals of calcium pyrophosphate dihydrate (CPPD, [Ca2{O(PO3)2}] 2H2O, triclinic + monoclinic forms) and on crystalline aggregates of menisci from patients affected by chondrocalcinosis (CC). Synthetic CPPD crystals were incubated with the different polyphosphates in phosphate buffered saline (PBS) for 1 hour at 37oC. Calcified menisci were obtained from the knees of 4 female patients with CPPD deposition disease who had undergone total arthroscopic meniscectomy for degenerative meniscal lesions. The dissolution of CPPD crystals by polyphosphates was assessed by atomic absorption spectroscopy (AAS), determining the amount of calcium liberated from synthetic crystals as well as meniscal fragments. At the same concentration of phosphate ions, SMP and PSTP showed higher DA (mean + SD: 24.1 + 3.0 m g/ml and 21.7 + 4.3 mg/ml, respectively) on CPPD crystals than TSMP (1.6 + 0.5 mg/ml). Macroscopic and microscopic evaluations of meniscal specimens showed a notable decrease in CPPD deposits.
Editorial Comment: The accumulation of CPPD crystals in articular tissue or synovial fluid has been associated with a variety of manifestations, from radiographic evidence of chondrocalcinosis to symptoms similar to acute gout-like inflammatory episodes, polyarticular inflammatory arthritis, or osteoarthritis. Currently, there are no available therapeutic agents that have the ability to prevent CPPD crystals accumulating or dissolving them when present. This study raises the possibility tht PSTP or SMP may be useful therapeutic agents for CPPD induced crystals.
