Abstract:
:Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases plasma low-density lipoprotein cholesterol (LDL-C) by decreasing expression of the LDL receptor on hepatic cells. Evolocumab is a human monoclonal immunoglobulin G2 that binds specifically to human PCSK9 to reduce LDL-C. Evolocumab exhibits nonlinear kinetics as a result of binding to PCSK9. Elimination is predominantly through saturable binding to PCSK9 at lower concentrations and a nonsaturable proteolytic pathway at higher concentrations. The effective half-life of evolocumab is 11-17 days. The pharmacodynamic effects of evolocumab on PCSK9 are rapid, with maximum suppression within 4 h. At steady state, peak reduction of LDL-C occurs approximately 1 week after a subcutaneous dose of 140 mg every 2 weeks (Q2W) and 2 weeks after a subcutaneous dose 420 mg once monthly (QM), and returns towards baseline over the dosing interval. In several clinical studies, these doses of evolocumab reduced LDL-C by approximately 55-75% compared with placebo. Evolocumab also reduced lipoprotein(a) [Lp(a)] levels and improved those of other lipids in clinical studies. No clinically meaningful differences in pharmacodynamic effects on LDL-C were observed in adult subjects regardless of mild/moderate hepatic impairment, renal impairment or renal failure, body weight, race, sex, or age. No clinically meaningful differences were observed for the pharmacodynamic effects of evolocumab on LDL-C between patients who received evolocumab alone or in combination with a statin, resulting in additional lowering of LDL-C when evolocumab was combined with a statin. No dose adjustment is necessary based on patient-specific factors or concomitant medication use.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Kasichayanula S,Grover A,Emery MG,Gibbs MA,Somaratne R,Wasserman SM,Gibbs JPdoi
10.1007/s40262-017-0620-7subject
Has Abstractpub_date
2018-07-01 00:00:00pages
769-779issue
7eissn
0312-5963issn
1179-1926pii
10.1007/s40262-017-0620-7journal_volume
57pub_type
杂志文章,评审abstract::Part I of this article, which appeared in the previous issue of the Journal, covered the following agents: histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine); muscarinic-M1-receptor antagonists (pirenzepine); proton pump inhibitors (omeprazole); site-protective agents (colloidal bismuth...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199019020-00002
更新日期:1990-08-01 00:00:00
abstract:BACKGROUND:The imatinib trough plasma concentration (C(min)) correlates with clinical response in cancer patients. Therapeutic drug monitoring (TDM) of plasma C(min) is therefore suggested. In practice, however, blood sampling for TDM is often not performed at trough. The corresponding measurement is thus only remotely...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/11596990-000000000-00000
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abstract::Protein binding of antibacterials in plasma and tissues has long been considered a component of their pharmacokinetic parameters, playing a potential role in distribution, excretion and therapeutic effectiveness. Since the beginning of the 'antibacterial era', this factor has been extensively analysed for all antibact...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241100-00004
更新日期:2002-01-01 00:00:00
abstract::There are considerable laboratory data and information from animal and continuous culture in vitro models to support continuous infusion therapy for penicillins and cephalosporins, but, as yet, the only existing clinical data relate to cephalosporins. Penicillins do not exert concentration-dependent killing in the the...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199835050-00004
更新日期:1998-11-01 00:00:00
abstract:BACKGROUND:Duloxetine, a selective serotonin (5-hydroxytryptamine) and norepinephrine reuptake inhibitor, has been approved since 2004 for the treatment of adults with major depressive disorder (MDD). It is currently not approved for use in pediatric patients (aged <18 years) with MDD. The clinical development program ...
journal_title:Clinical pharmacokinetics
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doi:10.1007/s40262-014-0149-y
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abstract::Direct-acting antivirals (DAAs) are known victims (substrate) and perpetrators (cause) of drug-drug interactions (DDIs). These DAAs are used for the treatment of hepatitis C virus (HCV) infections and are highly effective drugs. Drugs used for cardiovascular risk management are frequently used by HCV-infected patients...
journal_title:Clinical pharmacokinetics
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abstract::Antipyrine pharmacokinetics were studied in 6 healthy women before and 2, 8 and 12 weeks after administering the injectable progestagen (progestin), norethisterone (norethindrone) enanthate 200mg intramuscularly. Additionally, antipyrine kinetics in 5 women who had previously used the injectable contraceptive for 8 to...
journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-198611020-00007
更新日期:1986-03-01 00:00:00
abstract:BACKGROUND:People living with human immunodeficiency virus are ageing under combination antiretroviral treatments but data on drug exposure in serum and cerebrospinal fluid are limited. Dolutegravir is a widely used second-generation integrase strand transfer inhibitor: conflicting data suggest that neuropsychiatric si...
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doi:10.1007/s40262-020-00916-9
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abstract:BACKGROUND:Reducing the dose of efavirenz can improve safety, reduce costs, and increase access for patients with HIV infection. According to the World Health Organization, a similar dosing strategy for all patient populations is desirable for universal roll-out; however, it remains unknown whether the 400 mg daily dos...
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doi:10.1007/s40262-018-0642-9
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.2165/00003088-197904020-00005
更新日期:1979-03-01 00:00:00
abstract::The pharmacokinetics and antihypertensive effects of felodipine, a new dihydropyridine calcium channel blocker, were studied in elderly hypertensive patients, 67 to 79 years of age and in young healthy subjects, 20 to 34 years of age following oral administration of 5 mg twice daily to steady-state. A single intraveno...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198814060-00004
更新日期:1988-06-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-016-0486-0
更新日期:2017-08-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198005040-00003
更新日期:1980-07-01 00:00:00
abstract::There are many pathological changes in patients with cystic fibrosis (CF) which can lead to alterations in drug disposition. Although, in patients with CF, the extent of drug absorption varies widely and the rate of absorption is slower, bioavailability is not altered. Plasma protein binding for the majority of drugs ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199835040-00004
更新日期:1998-10-01 00:00:00
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journal_title:Clinical pharmacokinetics
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doi:10.2165/11536630-000000000-00000
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Metformin is a biguanide used in the treatment of type 2 diabetes mellitus. In girls with a low birth weight, and early-normal and rapidly progressive puberty, metformin therapy is capable of modifying this outcome, prolonging pubertal growth, increasing height gain, delaying the age at menarch...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
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abstract::Interpatient pharmacokinetic variability normally observed in adults is often of even greater magnitude in paediatric patients because of age-related maturation of physiological processes responsible for drug disposition. Several antineoplastic agents have shown age-related changes, including alterations in volume of ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
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doi:10.2165/00003088-198207050-00005
更新日期:1982-09-01 00:00:00
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abstract:: ...
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pub_type: 评论,信件
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
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abstract:BACKGROUND AND OBJECTIVE:Daclizumab high-yield process (DAC HYP) is a humanized monoclonal antibody that selectively blocks the α-subunit (CD25) of the high-affinity interleukin-2 receptors, and has shown robust efficacy as a treatment for multiple sclerosis (MS). This work quantitatively characterized the relationship...
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pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-015-0305-z
更新日期:2016-01-01 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
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更新日期:1993-01-01 00:00:00
abstract::Clarithromycin is a semisynthetic macrolide antibiotic, structurally related to erythromycin. It has a more favourable pharmacokinetic profile than erythromycin, thus allowing twice-daily administration and possibly increasing compliance among outpatients. Clarithromycin is well absorbed from the gastrointestinal trac...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199325030-00003
更新日期:1993-09-01 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::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
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更新日期:1990-06-01 00:00:00
abstract::The effects of age and gender on the single and multiple dose pharmacokinetics of zileuton have been examined in a phase I nonblinded study. A total of 27 healthy volunteers were evaluable, 9 in the young group (age range 20 to 40 years; 5 males and 4 females) and 18 in the elderly group (range 65 to 81 years; 9 males...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
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更新日期:1995-01-01 00:00:00
abstract::Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-013-0103-4
更新日期:2013-12-01 00:00:00