Retrospective study of salazosulfapyridine in eight patients with rheumatoid arthritis on hemodialysis

Abstract

Objective. We examined the pharmacokinetics (PK) of salazosulfapyridine (SASP) and its metabolite, sulfapyridine (SP), as well as the influence of hemodialysis (HD), and investigated the utility of consecutive administration of SASP in rheumatoid arthritis patients undergoing HD.

Methods. The PK of salazosulfapyridine and SP in serum samples from 8 patients was determined using high-performance liquid chromatography.

Results. When SASP 500 mg was administered, the area under curve for serum concentration of SASP was similar to that seen with normal subjects in the Phase I study. The maximum serum concentration of SP was significantly higher than that in normal subjects, but was far from the danger level. SASP was not dialyzed, whereas on average 62% of SP was dialyzed. Following 5 consecutive days of administration of SASP, serum levels of SASP and SP on day 5 were rather higher than those on day 1, although both remained within the safe range. SASP administration from four months to three years in seven subjects resulted in four American College of Rheumatology 20 improvement criteria (57.1%), with one developing a rash.

Conclusions. If SASP is initiated at a low dosage (≤ 500 mg) and increased up to 1000 mg under careful monitoring, it is safe for HD patients.

Keywords:

• Disease-modifying anti-rheumatic drugs
• End-stage renal disease
• Pharmacokinetics
• Salazosulfapyridine
• Sulfapyridine

Acknowledgements

We would like to thank Dr Yoshimasa Oka for his assistance with patient registrations, and Mr Hisashi Baba for his assistance with the measurements of SASP levels. Our heartfelt thanks also go to Professor Eiji Uchida of the Department of Pharmacology of Showa University for his advice concerning the handling of data from the Phase I study, to Professor Kei Maruyama of the Department of Pharmacology of Saitama Medical University for his advice concerning the calculation of pharmacokinetic parameters, and to Associate Professor Michio Shiibashi of the Saitama Medical University Medical Education Center for his advice concerning statistical analyses.

Conflicts of interest

T. Mimura has received research grants from Takeda Pharmaceutical Co., Ltd, Mitsubishi-Tanabe Pharma Corporation, Abbott Japan Co., Ltd., and Chugai Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.