Pharmacokinetics of Salazosulfapyridine (Sulfasalazine, SASP)(V):Pharmacokinetics of SASP after a single intravenous or oral administration in the dog.

Abstract

Salazosulfapyridine(Sulfasalazine, SASP) labelled with ¹⁴C in the carboxyl group and with ³H in the benzenesulfonyl ring was administered intravenously or orally to male and female beagle dogs with and without bile fistulas in order to study the pharmacokinetics. After intravenous administration a plasma elimination half life (t_1/2β) for SASP was calculated to 14 min. The volume of distribution (Vd_ss) was found to be 0.47l/kg and the total clearance was about 35ml/min × kg. After oral administration of 50, 250 or 500mg/kg the time for maximal plasma concentration of SASP was 1 ?? 3 hours and the maximal concentration was 2.81±1.42μM after a dose of 50mg/kg and 15.08±3.04μM after 500mg/kg body weight.
The bioavailability varied between 5.4 ?? 30% which is within the same range as reported from studies in man. The renal clearance was between 0.1 ?? 0.2l/min × kg.
Metabolites of SASP were separated by HPLC and identified by mass spectrometry. 5-aminosalicylic acid (5ASA), sulfapyridine (SP) and its glucuronide were found in plasma and urine. 5ASA, N-acetylated 5ASA (Ac5ASA), SP and unmetabolized SASP were found in faeces.
The cumulative biliary excretion of SASP after i.v. administration was as a mean 95% of the administered dose. Similar figures were obtained for the ¹⁴C and ³H radioactivity. Thus a quantitative excretion of the unchanged drug was found in the bile during 24 hours after administration and >90% was recovered during the first 2hours. No metabolites were found in the bile. After oral administration of SASP 18% of the administered dose was recovered as the unchanged drug in bile, 17% as ¹⁴C and 19% as ³H radioactivity within 48 hours. As after intravenous administration no metabolites were found in bile after the oral administration.
The total recovery of excreted radioactivity after i.v. and oral administration was 69 ?? 96%. The tritium radioactivity representing the SP metabolites was mainly found in urine, while carbon-14 representing SASP and 5ASA metabolites was preferentially excreted in fae ces. This is in accordance with the higher absorption of SP and its metabolites, compared to 5ASA which is poorly absorbed and thus mainly eliminated via faeces together with a small amount of unchanged SASP.