Evaluation of gender in the oral pharmacokinetics of clindamycin in humans

Carrasco-Portugal, Miriam del Carmen; Luján, Miguel Ángel; Flores‐Murrieta, Francisco J.

doi:10.1002/bdd.624

Cited by 21 publications

(12 citation statements)

References 13 publications

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“…[23][24][25] Although several studies report higher CYP3A activity in women, 26-28 others found no sex effect. 29 Our results indicate that sex plays an important role on CYP3A activity and quinine disposition. In contrast to our findings, Mirghani et al did not find a sex effect on quinine metabolic ratio in Tanzanians.…”

Section: Discussionmentioning

confidence: 63%

Genetic Variations in ABCB1 and CYP3A5 as well as Sex Influence Quinine Disposition Among Ugandans

Mukonzo¹,

Waako²,

Ogwal-Okeng³

et al. 2010

Therapeutic Drug Monitoring

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Quinine is one of the most effective antimalarial drugs, although its clinical use is limited as a result of its narrow safety margin. Quinine is a substrate of the polymorphic p-glycoprotein and CYP3A4/3A5. This study aimed to examine the effects of genetic variations in ABCB1 and CYP3A5 genes, sex, demographic, and biochemical variables (serum albumin, creatinine, alanine aminotransferase and albumin) on quinine disposition among Ugandans. Quinine (600 mg) was orally administered to 140 healthy volunteers. Quinine and its metabolite 3-hydroxyquinine concentrations were determined from 16-hour postdose plasma by high-performance liquid chromatography. CYP3A5 activity was measured using quinine/3-hydroxyquinine ratio (metabolic ratio). Genotyping for a total of 20 single nucleotide polymorphisms in ABCB1 (n = 13) and CYP3A5 (n = 7) was done using Taqman and minisequencing on microarray. There were 20.5- and 13-fold variations in body weight-adjusted plasma quinine concentrations (mean +/- standard deviation, 5.26 +/- 2.5 mumol/L; range, 0.88-18.10 mumol/L) and quinine-to-3-hydroxyquinine metabolic ratio (mean +/- standard deviation, 7.68 +/- 3.3 mumol/L; range, 1.66-22.3 mumol/L), respectively. Weight-adjusted plasma quinine concentration was significantly influenced by sex and ABCB1 haplotype. There was a significant sex difference in quinine metabolic ratio, women being faster metabolizers than men (P = 0.01). CYP3A5 genotype/haplotype significantly (P = 0.03) influenced quinine disposition with a clear CYP3A5*1 gene dose effect. The result confirms that quinine disposition is influenced mainly by sex as well as by ABCB1 and CYP3A5 genotypes. Despite being fast metabolizers, women display higher quinine bioavailability than men in Uganda. This may have clinical significance in determining an individual's susceptibility to quinine-associated adverse reactions such as cinchonism.

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Section: Discussionmentioning

confidence: 63%

Genetic Variations in ABCB1 and CYP3A5 as well as Sex Influence Quinine Disposition Among Ugandans

Mukonzo¹,

Waako²,

Ogwal-Okeng³

et al. 2010

Therapeutic Drug Monitoring

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“…For example, women exhibited higher plasma concentrations of the antibacterial drug clindamycin than men in one study after an oral 600 mg dose, but these concentrations were similar when normalized for body weight (del Carmen Carrasco-Portugal et al 2008). A similar study demonstrated that after a single oral 200 mg dose of fluconazole, a commonly used antifungal drug, in healthy Chinese adults, sex-related differences in AUC, C max , and volume of distribution which directly correlated with body weight were observed .…”

Section: Distributionmentioning

confidence: 92%

Sex and Gender Differences in Infection and Treatments for Infectious Diseases

Klein

Roberts

2015

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This book provides an overview of the underlying sex-based and hormone-based differences in immunity, wound healing and pharmacokinetics, while also exploring how pregnancy affects immunity. The second part of the book shows, for the first time in a single volume, the growing number of infectious diseases for which sex and gender differences are noted, identifies common as well as distinct mechanisms mediating these differences and illustrates how responses to treatments might differ between the sexes. The awareness that males and females differ in their response to specific pathogens as well as to treatments for infectious diseases may yield sex-specific personalized treatments. This book will be of interest to basic scientists and clinicians in the fields of microbiology, immunology and pharmacology. Individuals working in academia, government and industry will also benefit from the information presented

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“…It has been described that activity of this isozyme is 20 to 50% higher in women when compared with men [45]. However, other authors have not found any difference between genders when oral pharmacokinetics of drugs has been compared [47,53,54]. Additionally to these studies, it has been evaluated the differences in the urinary excretion of 6-betahydroxycortisol/cortisol (a marker of hepatic CYP3A4) in Asian and Caucasian women [55].…”

Section: Metabolismmentioning

confidence: 99%

Gender Differences in the Pharmacokinetics of Oral Drugs

Carrasco-Portugal¹,

Flores‐Murrieta²

2011

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Establishment of rational dosage regimens requires the knowledge of pharmacokinetics and pharmacodynamics in the target population. It has been established that side effects produced by drugs are more frequent in women than in men. This may be due to two possibilities, one is that normalized dose received by women is higher than men and the other is that anatomical and physiological characteristics are a quite different. In this review, some aspects that may play a role in the generation of such differences are analyzed, including the impact on absorption, distribution, metabolism and excretion of drugs. Most of the changes can be explained by differences in volume of distribution and systemic clear- ance, however, presystemic clearance also seems to play a role in such dissimilarities. The final result, in general, is that women have higher plasma levels of drugs and usually these differences are reduced or abolished when data are normalized by the body weight, since both, volume of distribution and systemic clearance are influenced by it; however, there are some cases in which differences remain. Further research oriented to establish the role of each of the ana- tomical and physiological differences in the oral pharmacokinetics of drugs is warranted

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Evaluation of gender in the oral pharmacokinetics of clindamycin in humans

Cited by 21 publications

References 13 publications

Genetic Variations in ABCB1 and CYP3A5 as well as Sex Influence Quinine Disposition Among Ugandans

Genetic Variations in ABCB1 and CYP3A5 as well as Sex Influence Quinine Disposition Among Ugandans

Sex and Gender Differences in Infection and Treatments for Infectious Diseases

Gender Differences in the Pharmacokinetics of Oral Drugs

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