Gender differences in pharmacokinetics and pharmacodynamics of azosemide in rats

Lee, Young S.; Han, Kyung-Sook; Lee, Myung G.

doi:10.1002/(sici)1099-081x(199905)20:4<225::aid-bdd176>3.0.co;2-e

Cited by 8 publications

(2 citation statements)

References 17 publications

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“…Women and men exhibit different responses to treatments due to variations in physiological, anatomical, and hormonal characteristics. The disparities in therapeutic agent pharmacokinetics and pharmacodynamics play a crucial role in determining the effectiveness of treatments ( Beierle et al, 1999 ; Bies et al, 2003 ; Bigos et al, 2009 ; Chen, 2005 ; Dawkins and Potter, 1991 ; Dawkins et al, 1993 ; Gandhi et al, 2004 ; Marazziti et al, 2013 ; Regitz-Zagrosek, 2014 ; Zucker and Prendergast, 2020 ; Fletcher et al, 1994 ; Franconi and Campesi, 2017 ; Frost et al, 2015 ; Anderson, 2008 ; Anthony and Berg, 2002 ; Flores Pérez et al, 2003 ; Franconi et al, 2007 , 2011a ; Greenblatt et al, 2004 , 2014 ; Gupta et al, 1995 ; Harris et al, 1995 ; Jiang et al, 2015 ; Krecic-Shepard et al, 2000 ; Lee et al, 1999 ; Luzier et al, 1999 ; Patrick et al, 2007 ; Soldin and Mattison, 2009 ; Song et al, 2018 ; Swan and Hursting, 2000 ; Tamargo et al, 2017 ; Thürmann and Hompesch, 1998 ; Ueno and Sato, 2012 ; Vachharajani et al, 2011 ; Yonkers et al, 1992 ; Yoon et al, 2021 ). Although the gender differences in pharmacology were recognized as early as 1932 with the study on barbiturates in rats, a comprehensive understanding of the significance of gender pharmacology only emerged towards the end of the last century ( Gandhi et al, 2004 ; Franconi et al, 2007 , 2011a , 2011b ; Anderson, 2005 ).…”

Section: Resultsmentioning

confidence: 99%

The relationship between gender and pharmacology

Younes

2024

Current Research in Pharmacology and Drug Discovery

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Section: Resultsmentioning

confidence: 99%

The relationship between gender and pharmacology

Younes

2024

Current Research in Pharmacology and Drug Discovery

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“…Women and men respond differently to treatments; this mainly depends on physiological, anatomical, and hormonal characteristics. The existence of the differences in therapeutic agent pharmacokinetics and pharmacodynamics influences the response to treatments [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. Although this was already known since 1932, the year in which the first study on the gender difference in the pharmacology of barbiturates in rats was reported, full awareness of the relevance of the role of gender pharmacology only came at the end of the last century [ 16 , 26 , 27 , 46 , 47 ].…”

Section: Gender-specific Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

Evaluation of Sex Differences in Preclinical Pharmacology Research: How Far Is Left to Go?

Allegra,

Chiara,

Di Grazia

et al. 2023

Pharmaceuticals

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Until the last quarter of the 20th century, sex was not recognized as a variable in health research, nor was it believed to be a factor that could affect health and illness. Researchers preferred studying male models for a variety of reasons, such as simplicity, lower costs, hormone confounding effects, and fear of liability from perinatal exposure in case of pregnancy. Equitable representation is imperative for determining the safety, effectiveness, and tolerance of therapeutic agents for all consumers. Decades of female models’ underrepresentation in preclinical studies has resulted in inequality in the understanding, diagnosis, and treatment of disease between the sexes. Sex bias has been highlighted as one of the contributing factors to the poor translation and replicability of preclinical research. There have been multiple calls for action, and the inclusion of sex as a biological variable is increasingly supported. However, although there has been substantial progress in the efforts to include more female models in preclinical studies, disparities today remain. In the present review, we consider the current standard practice of the preclinical research setting, why the sex bias exists, why there is the need to include female models, and what risks may arise from continuing this exclusion from experimental design.

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Pharmacokinetics and pharmacodynamics of azosemide

Suh¹,

Kim²,

Lee³

2003

Biopharm & Drug Disp

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Azosemide is used in the treatment of oedematous states and hypertension. The exact mechanism of action is not fully understood, but it mainly acts on both the medullary and cortical segments of the thick ascending limb of the loop of Henle. Delayed tolerance was demonstrated in humans by homeostatic mechanisms (principally an increase in aldosterone secretion and perhaps also an increase in the reabsorption of solute in the proximal tubule). After oral administration to healthy humans in the fasting state, the plasma concentration of azosemide reached its peak at 3-4 h with an absorption lag time of approximately 1 h and a terminal half-life of 2-3 h. The estimated extent of absolute oral bioavailability in humans was approximately 20.4%. After oral administration of the same dose of azosemide and furosemide, the diuretic effect was similar between the two drugs, but after intravenous administration, the effect of azosemide was 5.5-8 times greater than that in furosemide. This could be due to the considerable first-pass effect of azosemide. The protein binding to 4% human serum albumin was greater than 95% at azosemide concentrations ranging from 10 to 100 microg/ml using an equilibrium dialysis technique. The poor affinity of human tissues to azosemide was supported by the relatively small value of the apparent post-pseudodistribution volume of distribution (Vdbeta), 0.262 l/kg. Eleven metabolites (including degraded products) of azosemide including M1, glucuronide conjugates of both M1 and azosemide, thiophenemethanol, thiophencarboxylic acid and its glycine conjugate were obtained in rats. Only azosemide and its glucuronide were detected in humans. In humans, total body clearance, renal clearance and terminal half-life of azosemide were 112 ml/min, 41.6 ml/min and 2.03 h, respectively. Azosemide is actively secreted in the renal proximal tubule possibly via nonspecific organic acid secretory pathway in humans. Thus, the amount of azosemide that reaches its site of action could be significantly modified by changes in the capacity of this transport system. This capacity, in turn, could be predictably changed in disease states, resulting in decreased delivery of the diuretic to the transport site, as well as in the presence of other organic acids such as nonsteroidal anti-inflammatory drugs which could compete for active transport of azosemide. The urinary excretion rate of azosemide could be correlated well to its diuretic effects since the receptors are located in the loop of Henle. The diuretic effects of azosemide were dependent on the rate and composition of fluid replacement in rabbits; therefore, this factor should be considered in the evaluation of bioequivalence assessment.

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Gender differences in pharmacokinetics and pharmacodynamics of azosemide in rats

Cited by 8 publications

References 17 publications

The relationship between gender and pharmacology

The relationship between gender and pharmacology

Evaluation of Sex Differences in Preclinical Pharmacology Research: How Far Is Left to Go?

Pharmacokinetics and pharmacodynamics of azosemide

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