The pharmacokinetics of sulphasalazine in young and elderly patients with rheumatoid arthritis.
The clinical pharmacokinetics of enteric-coated sulphasalazine (Salazopyrin-EN) were studied after acute and chronic dosing in 20 patients with 'active' rheumatoid arthritis. 12 elderly (mean age 74.4 +/- 1 yr; range 71-83) and 8 young (mean age 40.5 +/- 1.4 yr; range 35-46) patients were given a single 2 g oral dose of sulphasalazine after an overnight fast. Serum and urine samples were collected at regular intervals over a 96 hour period for estimation of concentrations of sulphasalazine, sulphapyridine and its metabolites. This procedure was repeated after 17 days of continuous treatment with salazopyrin-EN 2 g daily in order to compare the drug's kinetics at 'steady-state'. Whilst the interindividual variation in kinetic parameters was large, age and acetylator status had a significant influence on a number of factors. The elimination half-life of sulphasalazine was prolonged in the elderly whilst renal clearance was increased in slow acetylators at 'steady-state'. The tmax and apparent volume of distribution of sulphapyridine were increased in the elderly after a single drug dosage but these differences disappeared with regular dosing. The Cmax, elimination half-life, 'steady-state' serum concentration, apparent volume of distribution and total clearance of sulphapyridine were all affected by acetylator status. We conclude that old age has only a minor effect on the body's handling of sulphasalazine and sulphapyridine but that acetylator phenotype plays a significant role in determining the 'steady-state' serum concentrations of sulphapyridine. This is likely to have practical implications with regard to some of the drug's adverse effects.
D000107:Acetylation; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D010641:Phenotype; D013427:Sulfapyridine / Q000493:pharmacokinetics; D012460:Sulfasalazine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013608:Tablets, Enteric-Coated
D013608:Tablets, Enteric-Coated; D012460:Sulfasalazine; D013427:Sulfapyridine