Abstract:
:The present article should be read in conjunction with the original review published in the Journal in 1983. There is no new information of major significance about the pharmacokinetics of levonorgestrel, norethisterone (norethindrone) or ethinylestradiol, although it has been shown that the concentrations of these hormones secreted in breast milk are small and mothers taking combined oral contraceptive steroids may breast-feed safely. Both levonorgestrel and ethinylestradiol can be successfully administered from appropriate vaginal formulations, but no clear advantages over oral administration have been demonstrated. Several new progestogens have been investigated. Desogestrel is a prodrug for its active metabolite 3-keto-desogestrel, gestodene is itself an active progestogen and norgestimate is a prodrug acting by conversion to norgestrel and its metabolites. All 3 compounds have good bioavailability with wide intersubject variation. The newer progestogens, like norethisterone and levonorgestrel, are bound to sex hormone binding globulin (SHBG). This causes their plasma concentrations to increase with time, since SHBG is induced by ethinylestradiol even in doses of 30 micrograms daily. The binding capacity and affinity of SHBG do not increase in direct proportion to its concentration. Further drug interactions with oral contraceptive steroids have been described. Contraceptive steroids may inhibit hepatic microsomal enzyme metabolism and increase the plasma concentration and effect of some tricyclic antidepressants, the hydroxylated benzodiazepines, some beta-blocking drugs, methylxanthines, prednisolone and cyclosporin. There are no significant effects on vitamins. Oral contraceptive steroids induce glucuronidation and hence decrease plasma concentrations of some benzodiazepines, clofibric acid, paracetamol (acetaminophen) and possibly morphine. The plasma concentration of ethinylestradiol may be increased by competitive sulphation with paracetamol. Plasma concentrations of contraceptive steroids are decreased by griseofulvin, which induces their hepatic metabolism. The role of other antibiotics remains controversial but there is probably a group of susceptible women who have lower plasma contraceptive hormone concentrations and experience breakthrough bleeding or pregnancy when given broad spectrum antibiotics. This may relate to interruption of the enterohepatic recirculation of ethinylestradiol. Anticonvulsants, other than valproic acid, all induce contraceptive steroid metabolism and therefore lower plasma hormone concentrations, thus reducing contraceptive effectiveness.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Shenfield GM,Griffin JMdoi
10.2165/00003088-199120010-00002subject
Has Abstractpub_date
1991-01-01 00:00:00pages
15-37issue
1eissn
0312-5963issn
1179-1926journal_volume
20pub_type
杂志文章,评审abstract::A large body of evidence suggests that not only direct anticoagulant effects but also major bleeding events and stroke prevention depend on plasma concentrations of direct oral anticoagulants (DOACs). Concomitant drugs that cause drug-drug interactions (DDIs) alter DOAC exposure by increasing or decreasing DOAC bioava...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-020-00879-x
更新日期:2020-08-01 00:00:00
abstract::Hepatic and renal insufficiency due to co-infection, alcoholism, diabetes mellitus, family history, adverse effects of antiretrovirals and other factors are commonly seen in HIV-infected patients. Therefore, the use of antiretrovirals in this patient setting requires attention to the pharmacokinetic issues that clinic...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200847030-00002
更新日期:2008-01-01 00:00:00
abstract::Aminoglycoside antibiotics are very important in the treatment of Gram-negative infections and as synergistic agents for the treatment of staphylococcal and streptococcal (group B streptococci and enterococci) infections. However, these agents have a narrow therapeutic index. Thus, a number of new antibiotics have bee...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199426010-00006
更新日期:1994-01-01 00:00:00
abstract::Over the past few decades, the importance of applying pharmacokinetic principles to the design of drug regimens has been increasingly recognised by clinicians. From the perspective of antimicrobial chemotherapy, an improvement in clinical outcome and/or a reduction in toxicity are of primary interest. Before applicati...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199937010-00001
更新日期:1999-07-01 00:00:00
abstract::Most of the currently available psychotropic drugs form 1 or more active metabolites during in vivo biotransformation in humans and/or animals. In some cases these metabolites are rapidly conjugated and excreted, but in others they attain blood and/or brain concentrations within the same range as, or even higher than,...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199018060-00002
更新日期:1990-06-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Genetic polymorphisms of cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) and patient demographic characteristics are responsible for inter-individual differences in warfarin maintenance dosage requirements. At present, however, the factors associate...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-012-0009-6
更新日期:2012-12-01 00:00:00
abstract::In the last 15 years the role of opioids in anaesthesia management has undergone dramatic change. Initially used as premedicants, or adjuvants to inhalation anaesthetic agents or as analgesics for postoperative pain relief, narcotics have now evolved into primary anaesthetic agents, primarily because of their ability ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198611010-00002
更新日期:1986-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Two phase I drug interaction studies were performed with oral enzalutamide, which is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). METHODS:A parallel-treatment design (n = 41) was used to evaluate the effects of a strong cytochrome P450 (CYP) 2C8 inhib...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-015-0283-1
更新日期:2015-10-01 00:00:00
abstract::The half-life and metabolic clearance rate (MCR) of antipyrine and phenytoin were determined in 14 young (mean age: 28.8 +/- 8.3 (SD) years] and in 14 elderly [mean age: 83.5 +/- 7.1 (SD) years] subjects and correlated with liver volume, which was determined by ultrasonic scanning, to see if an age-dependent differenc...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198106050-00005
更新日期:1981-09-01 00:00:00
abstract::Dilevalol and labetalol are examples of a growing number of new beta-blockers which combine nonselective beta-adrenoceptor antagonism with vasodilator activity. Dilevalol is one of the 4 stereoisomers of labetalol, and is estimated to form approximately 25% of the racemic drug. Labetalol itself is an alpha 1-antagonis...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199121020-00002
更新日期:1991-08-01 00:00:00
abstract::In the drug therapy of cardiac emergencies, it is necessary to rapidly achieve therapeutic drug concentrations and adjust drug dose as the patient's clinical status changes. Cardiac dysfunction is often present and may alter drug pharmacokinetics. Circulatory failure causes sympathetically mediated vasoconstriction in...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198409040-00001
更新日期:1984-07-01 00:00:00
abstract::Pharmacological treatment of patients with Alzheimer's disease is becoming more important, as evidenced by the number of drugs being developed in different countries. It has been shown in the majority of clinical trials that cholinesterase inhibitors, such as tacrine (tetrahydroaminoacridine), are able to induce benef...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199529020-00005
更新日期:1995-08-01 00:00:00
abstract::Amiodarone is an iodinated benzofuran derivative with recognised antiarrhythmic activity in man. As yet, its pharmacokinetic behaviour has not been satisfactorily characterised. Specific and sensitive high-pressure liquid chromatographic methods have become available only recently and this partly explains the scarcity...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198409020-00002
更新日期:1984-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Losmapimod is an orally available, potent p38 mitogen-activated protein kinase inhibitor. It is in development as an anti-inflammatory drug in different therapeutic areas. Clinical studies have shown that losmapimod is well tolerated and safe in humans and several studies have shown its pharmac...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-012-0025-6
更新日期:2013-03-01 00:00:00
abstract::With the aging population and its rapidly increasing prevalence, dementia has become an important public health concern in developed and developing countries. To date, the pharmacological treatment is symptomatic and based on the observed neurotransmitter disturbances. The four most commonly used drugs are donepezil, ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-013-0038-9
更新日期:2013-04-01 00:00:00
abstract::Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as ind...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0573-x
更新日期:2018-02-01 00:00:00
abstract::The overall reporting rate of drug-drug interactions with fluvoxamine is very low: only 73 cases have been identified from an estimated exposure of over 8 million patients worldwide. The reporting rate is similar in men and women, and most events relate to the use of fluvoxamine in conjunction with psychotropic compou...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199500291-00006
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Upadacitinib is a janus kinase (JAK) 1 inhibitor being developed for the treatment of rheumatoid arthritis (RA) and other inflammatory diseases. This work characterized upadacitinib population pharmacokinetics in healthy subjects and RA patients and the effects of covariates on upadacitinib ex...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-017-0605-6
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:Fondaparinux sodium is a novel antithrombotic agent, the first of a new class of selective factor Xa inhibitors. It has favourable pharmacokinetics including 100% bioavailability, low variability and a mean terminal half-life of 17 hours for young and 21 hours for elderly healthy volunteers, enabling once-da...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200241002-00002
更新日期:2002-01-01 00:00:00
abstract::Dasabuvir is a nonstructural (NS) 5B non-nucleoside inhibitor of the hepatitis C virus (HCV) used in combination with ombitasvir/paritaprevir/ritonavir for the treatment of chronic HCV infection. It is primarily metabolized by cytochrome P450 (CYP) 2C8, with a minor contribution from CYP3A. Biotransformation of dasabu...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-017-0519-3
更新日期:2017-10-01 00:00:00
abstract::Doxycycline and minocycline are second-generation tetracyclines. They are readily absorbed, distributed throughout the organism as a function of their lipophilicity and eliminated in both the urine and the faeces. The influence of age, renal disease, malnutrition and hyperlipidaemia is reviewed, together with the main...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198815060-00001
更新日期:1988-12-01 00:00:00
abstract::Asthma is generally managed with bronchodilator therapy and/or anti-inflammatory drugs. Guidelines now advocate selection of drugs and pharmaceutical formulations (long-acting vs short-acting, inhaled vs systemic) on the basis of disease severity. Theophylline has a narrow therapeutic margin. Clearance is highly varia...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199426050-00006
更新日期:1994-05-01 00:00:00
abstract::In the treatment of patients with Parkinson's disease, apomorphine has an established place as a back-up therapy if other antiparkinsonian drugs, such as levodopa and oral dopamine agonists, have not controlled the existing response fluctuations. Apomorphine is a synthetic derivative of morphine, with a totally distin...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199937030-00004
更新日期:1999-09-01 00:00:00
abstract::It has been suggested that the minimum effective serum clozapine concentration for an acceptable clinical response (threshold value) is about 400 micrograms/L. This article argues against the use of therapeutic drug monitoring (TDM) as a tool to obtain clozapine concentrations of > or = 400 micrograms/L in the individ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199834060-00005
更新日期:1998-06-01 00:00:00
abstract::Fluconazole was recently developed for the treatment of superficial and systemic fungal infections. Triazole groups and insertion of 2 fluoride atoms increase the polarity and hydrosolubility of the drug, allowing it to be used in a parenteral form. Bioassay methods using Candida pseudotropicalis as a test organism we...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199324010-00002
更新日期:1993-01-01 00:00:00
abstract::The elderly are generally considered to be different from young people in terms of drug response and this applies particularly to quantitative differences. While altered drug handling is a major potential source of difference in responsiveness to drugs, the relative contribution of pharmacokinetics and pharmacodynamic...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-197601040-00003
更新日期:1976-01-01 00:00:00
abstract::Platelets contribute significantly to arterial-occlusive thrombosis, one of the major causes of death and disease throughout the world. Consequently, inhibiting platelet function is a potentially important therapeutic goal. Among agents that inhibit platelet function, ticlopidine shows a wide spectrum of antiplatelet ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199426050-00003
更新日期:1994-05-01 00:00:00
abstract::Peak expiratory flow rate, adverse effects and serum theophylline concentration were measured during treatment of episodes of severe airways obstruction. 174 patients were randomised to target theophylline concentrations of 10 mg/L or 20 mg/L. The recovery of peak flow rate towards normal values was explicable in term...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-199325060-00008
更新日期:1993-12-01 00:00:00
abstract::Short-term antimanic therapy with lithium and relapse-repressive, so-called "prophylactic" long-term therapy with lithium, may present clinical problems which demand an understanding of two cardinal properties of this form of therapy--the need to individualise the dose and the recognition that successful therapy invol...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-197702020-00001
更新日期:1977-03-01 00:00:00
abstract:BACKGROUND:Enzyme replacement therapy (ERT) is currently the standard treatment for patients with Gaucher disease type I (GD1), but the pharmacokinetics have hardly been studied. This study aimed to quantify in vivo enzyme activity in peripheral leukocytes from patients receiving long-term treatment with imiglucerase o...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0387-2
更新日期:2016-09-01 00:00:00