Renal clearance of sulphinpyrazone in man

Abstract

Six healthy young volunteers received a single dose of sulphinpyrazone 200 mg p.o. Plasma concentration and urinary excretion rate curves showed large intersubject variation for sulphinpyrazone and its metabolites. The sulphide metabolite could only be detected in plasma and not before 3-7 h after ingestion. The total recovery in urine of all compounds varied from 30-56% of the dose. In two subjects the mean residence time of sulphinpyrazone was twice as long as in the other subjects (10.4 h compared with 4.6 h), but the area under the plasma concentration-time curve was comparable to that in the others (mean: 3.0 mg X ml-1 X min), indicating that drug absorption was quantitatively similar but delayed. The renal clearance of sulphinpyrazone varied from 14-40 ml X min-1 (mean: 28 ml X min-1). In view of the very high plasma protein binding of sulphinpyrazone, active tubular secretion is the predominant mechanism in its renal clearance. The same holds for the sulphone metabolite, which has a mean renal clearance of 24 ml X min-1, and even more for the p-hydroxysulphinpyrazone metabolite, which has a renal clearance of 118 ml X min-1. No unambiguous evidence was found in favour of concentration-dependent renal clearance of sulphinpyrazone or its metabolites over the concentration range studied. The renal clearance, especially of sulphinpyrazone, appeared to be dependent on urine pH and not on urine flow rate.

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

“…It contains a chiral sulfoxide group and thus exists in two enantiomers. Like other sulfoxide-containing drugs, it is subject to both oxidation and reduction, with at least nine metabolites identified in human urine [1060][1061][1062]. Structurally, all the metabolites except one are compounds with the sulfur atom in various states of oxidation (sulfide, sulfoxide, or sulfone), either alone or in combination with a para-hydroxy N-phenyl group or a C 4 -glucuronide.…”

Expression and functions of N-type Cav2.2 and T-type Cav3.1 channels in rat vasopressin neurons under normotonic conditions

“…FFA has long been used therapeutically as one of the top prescribed non-steroidal anti-inflammatory drugs (NSAIDs) which exhibit anti-inflammatory, analgesic and antipyretic effects [ 37 ]. When 200 mg FFA was orally administered to young healthy persons, the peak plasma concentration was reported to reach 6 to 20 μg mL −1 , or 21 to 71 μM, within 1.5 h [ 38 ]. Since FFA was shown to largely suppress both T- and N-type VGCC currents at 70 and 100 μM in the present study in vitro, it is feasible that the endogenous VGCC activities, especially T-type one, in the axon terminal in situ are sometimes partially suppressed by the plasma FFA after oral administration, because the posterior pituitary region exists outside the blood–brain barrier [ 39 ].…”

N2‐Glucuronidation and N4‐acetylation of sulphaphenazole by the turtlePseudemys scripta elegans

“…These compounds become hydroxylated at the para (4) position of the phenyl group (4,7). By structural analogy such a para hydroxylation must also be possible for sulphaphenazole, which in turn may be followed by 0-glucuronidation and renal excretion.…”