Abstract：
:Oral contraceptives (OCs) are the most widely used form of birth control among women of childbearing potential. Knowledge of potential drug-drug interactions (DDIs) with OCs becomes imperative to provide information on the medication to women of childbearing potential and enable their inclusion in clinical trials, especially if the new molecular entity is a teratogen. Although a number of DDI guidance documents are available, they do not provide recommendations for the design and conduct of OC DDI studies. The evaluation of DDI potential of a new molecular entity and OCs is particularly challenging because of the availability of a wide variety of combinations of hormonal contraceptives, different doses of the ethinyl estradiol, and different metabolic profiles of the progestin component. The aim of this review is to comprehensively discuss factors to be considered such as pharmacokinetics (PK), pharmacodynamics (PD), choice of OC, and study population for the conduct of in vivo OC DDI studies. In this context, metabolic pathways of OCs, the effect of enzyme inhibitors and inducers, the role of sex hormone-binding globulin in the PK of progestins, current evidence on OC DDIs, and the interpretation of PD end points are reviewed. With the emergence of new tools like physiologically based PK modeling, the decision to conduct an in vivo study can be made with much more confidence. This review provides a comprehensive overview of various factors that need to be considered in designing OC DDI studies and recommends PK-based DDI studies with PK end points as adequate measures to establish clinical drug interaction and measurement of PD end points when there is basis for PD interaction.
journal_name
J Clin Pharmacoljournal_title
Journal of clinical pharmacologyauthors
Sun H,Sivasubramanian R,Vaidya S,Barve A,Jarugula Vdoi
10.1002/jcph.1765subject
Has Abstractpub_date
2020-12-01 00:00:00pages
S49-S62eissn
0091-2700issn
1552-4604journal_volume
60 Suppl 2pub_type
杂志文章abstract：:The benzothiadiazide diuretics are known to cause magnesium and potassium wasting and retention of calcium and uric acid. The effect of magnesium replacement on diuretic-induced changes in sodium, potassium, calcium, and magnesium balance, weight, and blood pressure was studied in 12 normal subjects and 13 hypertensiv...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1978.tb01582.x
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abstract：:Amiodarone is a unique antiarrhythmic agent originally developed as a vasodilator. Classified electrophysiologically as a Type III antiarrhythmic, it also has both nonspecific antisympathetic and direct, fast channel-membrane effects. Hemodynamic effects of orally administered amiodarone (a negative inotropic agent) a...
journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1002/j.1552-4604.1991.tb03673.x
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abstract：:The objective of this study was to evaluate the effect of the antireflux barrier formed by Na alginate on pH-metry-defined acid reflux events in preterms. Four times/day, 1 mL/kg of Na alginate was administered as an intervention to the preterm infants whose gastroesophageal reflux disease was confirmed by 24-hour pH ...
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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abstract：:Thirty-eight ambulatory patients with congestive cardiac failure took part in a double-blind clinical trial of 50 mg hydrochlorothiazide orally daily and slow-release formulation of 60 mg furosemide orally daily. Following a one-week period of placebo administration, patients were randomly allocated to the treatment w...
journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1982-11-01 00:00:00
abstract：:Lemborexant is a novel orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia. This article describes the population pharmacokinetics (PK) of lemborexant and the relationship of its daily steady-state exposure (Cav,ss ) to the probability of most frequent treatment-emergent ad...
journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1991.tb03659.x
更新日期：1991-10-01 00:00:00
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pub_type： 杂志文章,随机对照试验
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更新日期：2012-09-01 00:00:00
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1002/j.1552-4604.1993.tb03932.x
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,评审
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journal_title：Journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
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更新日期：1991-04-01 00:00:00
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journal_title：Journal of clinical pharmacology
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更新日期：2010-12-01 00:00:00
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1999-11-01 00:00:00
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
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journal_title：Journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1002/j.1552-4604.1984.tb02779.x
更新日期：1984-05-01 00:00:00
