The effect of diflunisal on the elimination of triamterene in human volunteers.
A major metabolic pathway for triamterene (a potassium sparing diuretic) is aromatic hydroxylation followed by sulphate conjugation. Diflunisal (a salicylate anti-inflammatory agent) also undergoes sulphate conjugation of its phenolic group as a major pathway. We investigated the possible effect of diflunisal on the elimination of triamterene (competition for phenolic sulphonation) in six healthy volunteers by studying the disposition of single doses of triamterene (100 mg) taken alone and in the presence of steady-state levels of diflunisal. Diflunisal coadministration (500 mg b.i.d.) had no effect on the pharmacokinetics of triamterene itself. However, plasma AUC of p-hydroxytriamterene sulphate was greater (4.6 times), and its renal clearance lower (0.24 times), in the presence of diflunisal. There was no change in the formation clearance or protein binding of p-hydroxytriamterene sulphate in the presence of diflunisal. The data point to competition for renal excretory pathways rather than sulphonation capacity. This interaction could have clinical relevance since p-hydroxytriamterene sulphate is pharmacologically active.
Jacob
S S
SS
Centre for Studies in Drug Disposition, University of Queensland, Royal Brisbane Hospital, Brisbane 4029 Queensland, Australia.
Franklin
M E
ME
Dickinson
R G
RG
Hooper
W D
WD
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004061:Diflunisal / Q000494:pharmacology*; D004232:Diuretics / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014223:Triamterene / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D004232:Diuretics; D004061:Diflunisal; D014223:Triamterene