Sex-difference and the effects of smoking and oral contraceptive steroids on the kinetics of diflunisal

• Published in: European journal of clinical pharmacology Vol. 38; no. 2; p. 175
• Main Authors: Macdonald, J I, Herman, R J, Verbeeck, R K
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1990
• Subjects: Adult; Blood Proteins - metabolism; Chromatography, High Pressure Liquid; Contraceptives, Oral, Hormonal - adverse effects; Diflunisal - metabolism; Diflunisal - pharmacokinetics; Female; Glucuronates - metabolism; Half-Life; Humans; Male; Protein Binding; Sex Factors; Smoking - metabolism; Sulfates - metabolism; Drugs > administraction and dosage; Laboratory Examinations And Diagnoses; Smoking > side effects; Oral Contraceptives > side effects; Contraception; Data Collection; Contraceptive Methods > side effects; Family Planning; Research Methodology; Examinations And Diagnoses; Treatment; Drugs > pharmacodynamics; Population Characteristics; Sex Factors; Data Analysis; Population; Behavior; Demographic Factors
• ISSN: 0031-6970
• DOI: 10.1007/BF00265980

The single dose pharmacokinetics of diflunisal were studied in 4 groups of 6 young volunteers: control men, control women, women taking low estrogen oral contraceptive steroids (OCS), and women smokers (10-20 cigarettes day). The plasma clearance of diflunisal was significantly higher in men (0.169 ml.min-1.kg-1) and in women on OCS (0.165 ml.min-1.kg-1) as compared to control women (0.108 ml.min-1.kg-1). Partial metabolic clearances of diflunisal by the three conjugative pathways (phenolic and acyl glucuronide formation, sulphate conjugation) were all increased in men and women OCS users as compared to control women. Statistically significant increases, however, were only observed for the partial metabolic clearance of diflunisal by phenolic glucuronidation between men and women (2.91 vs. 1.85 ml.min-1 respectively), and for the partial clearance by acyl glucuronidation between OCS users and control women (4.81 vs. 3.01 ml.min-1 respectively). Smoking resulted in a moderate increase (35%) in plasma diflunisal clearance. However, a significant reduction in total urinary recovery of diflunisal and its glucuronide and sulphate conjugates was found in smokers (70.5% in smokers as compared to 84.2-87.2% in the 3 other study groups). Consequently, smoking may have induced hydroxylation, a minor oxidative metabolic pathway of diflunisal recently discovered in man.