Effects of gender on the pharmacokinetics of drugs secreted by the renal organic anions transport systems in the rat

• Published in: Pharmacological research Vol. 45; no. 2; pp. 107 - 112
• Main Authors: Cerrutti, Jorgelina A., Quaglia, Nora B., Brandoni, Anabel, Torres, Adriana M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-02-2002
• Subjects: Animals; Anions; Biological Transport; Female; Furosemide - blood; Furosemide - pharmacokinetics; Furosemide - urine; Kidney - secretion; Male; organic anions, sex, pharmacokinetics, renal clearance, systemic clearance; p-Aminohippuric Acid - blood; p-Aminohippuric Acid - pharmacokinetics; p-Aminohippuric Acid - urine; Rats; Rats, Wistar; Sex Factors; organic anions, sex, pharmacokinetics, renal clearance, systemic clearance
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.2001.0912

The importance of considering sex differences in drug handling studies was admitted recently. The present work evaluates the sex influences on the pharmacokinetics of para-aminohippuric acid (PAH), the reference substance for the renal organic anion transports systems, and furosemide (FS), a standard loop diuretic which is also a substrate for this transport system. Female rats displayed a lower PAH and FS systemic clearance, and a lower value of the elimination rate microconstant from the central compartment for both drugs. These results may be explained by the diminution of the renal clearance of both PAH and FS observed in females. In summary, sex modifies the pharmacokinetics of organic anions. Although additional experimental work must be done to bridge the gap between studies using animals and humans, the reported experimental observations may have potentially important pharmacological implications. So, caution must be exercised in administering drugs like organic anions to females.