抄録
Salazosulfapyridine (Sulfasalazine, SASP, 2-hydroxy-5-[[4-[(2-pyridinylamino) sulfonyl] phenyl] azo] benzoic acid) labelled with 14C in the carboxyl group and with 3H in chemically as well as metabolically stable positions in the benzenesulfonyl ring was administered either intravenously or orally to male and female rats in order to study the plasma pharmacokinetics of SASP and the plasma profiles of the metabolites. After intravenous administration SASP was eliminated rapidly from plasma with a half-life (t1/2) of 8min. The volume of distribution (Vdss) of SASP was 0.2l/kg and total clearance (CLtot) was 18ml/min × kg. After oral administration, SASP was present in plasma mainly during the first 4 hours. The time for maximal concentration (Tmax) varied for SASP between 1 ?? 3 hours, for 14C, corresponding to 5ASA metabolites, between 3 ?? 10 hours and for 3H, corresponding to sulfapyridine metabolites, between4 ?? 12 hours. The inter-individual variation was considerable. The bioavai lability of SASP was 9% and independent of the dose. The maximal concentration(Cmax) and area under the curve (AUC) increased proportionally with the dose. The absorption of SASP was not influenced by fasting overnight.
There was a clear sex difference in the metabolism of SASP. The plasma concentration of sulfapyridine metabolites in female rats was twice that in male rats. No hydroxylated metabolites were found in female rat plasma, whereas in the male rats, the hydroxylated sulfapyridine metabolites were the major metabolites.
