Abstract:
BACKGROUND:Telbivudine (LdT) is an L-nucleoside that is structurally related to lamivudine. It is highly selective for hepatitis B virus (HBV) and inhibits viral DNA synthesis. LdT was approved by the US Food and Drug Administration on October 25, 2006, for the treatment of chronic HBV infection in adults who have active viral replication and either elevations in liver transaminases or signs of active liver disease on histologic examination. OBJECTIVE:This article reviews the pharmacology, pharmacokinetics, and therapeutic efficacy of LdT. Potential drug interactions and adverse events associated with the use of LdT are also reviewed. METHODS:Relevant publications were identified from searches of MEDLINE (1996-June 2007), the Cochrane Library, and BIOSIS (1993-June 2007). Search terms included, but were not limited to, telbivudine, beta-L-thymidine, LdT, pharmacology, pharmacokinetics, adverse events, resistance, drug interactions, hepatitis B, and therapeutic use. Additional publications were identified from the reference lists of the identified papers, meeting abstracts, and correspondence with the manufacturer of LdT. RESULTS:After 52 weeks of therapy in the Phase III GLOBE study, HBV resistance (breakthrough and resistance mutations) to LdT occurred in 3% of patients who were hepatitis B e antigen (HBeAg) positive and 2% of patients who were HBeAg negative. After 104 weeks of therapy, 17.8% to 21.6% of HBeAg-positive and 7.3% to 8.6% of HBeAg-negative LdT-treated patients had a rebound in HBV DNA associated with breakthrough and resistance mutations. After 24 weeks of treatment, the risk of resistance was greater in patients with HBV DNA titers >3 log(10) copies/mL than in those with lower numbers of copies. LdT is not active against lamivudine-resistant HBV. The proportion of HBeAg-positive patients with undetectable HBV DNA (by polymerase chain reaction assay) after 104 weeks of therapy in the GLOBE study was significantly greater with LdT compared with lamivudine (56% vs 39%, respectively; P < 0.05). After 104 weeks of therapy, the corresponding proportions of HBeAg-negative patients with undetectable HBV DNA were 82% and 57% (P < 0.05). Patients who failed lamivudine therapy in the GLOBE study showed cross-resistance to LdT. The most common adverse events associated with LdT are upper respiratory tract infection (14%-17%), fatigue and malaise (12%-14%), nasopharyngitis (11%-15%), headache (11%-12%), and abdominal pain (6%-12%). Grade 3/4 adverse events included elevations in serum creatine kinase, which were more common in patients receiving LdT than in those receiving lamivudine (9% vs 3%, respectively). Elevations in creatine kinase are typically asymptomatic; however, myopathy has been reported in 3 of 680 patients receiving LdT. CONCLUSIONS:LdT joins the increasing number of antiviral agents for the management of chronic HBV infection. Questions concerning the optimal length of therapy and long-term efficacy await the results of on-going clinical trials. Concerns about increasing resistance over time may relegate LdT to second-line status in the management of chronic HBV infection. The role of LdT in combination therapy is under investigation.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Matthews SJdoi
10.1016/j.clinthera.2007.12.032subject
Has Abstractpub_date
2007-12-01 00:00:00pages
2635-53issue
12eissn
0149-2918issn
1879-114Xpii
S0149-2918(07)00419-5journal_volume
29pub_type
杂志文章,评审abstract:BACKGROUND:Valproic acid has been associated with a highly variable intersubject absorptive phase; therefore, magnesium salt (magnesium valproate [MgV]) was developed to diminish variation during enteric absorption. OBJECTIVES:The aims of this study were to assess the pharmacokinetics of single oral doses of MgV 500-m...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2009.09.016
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:Apixaban (5 mg BID), dabigatran (available as 150 mg and 110 mg BID in Europe), and rivaroxaban (20 mg once daily) are 3 novel oral anticoagulants (NOACs) currently approved for stroke prevention in patients with atrial fibrillation (AF). OBJECTIVE:The objective of this study was to evaluate the cost-effect...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2013.12.011
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:Oral bisphosphonates are well established for the treatment and prevention of postmenopausal osteoporosis; however, they are poorly absorbed from the gastrointestinal (GI) tract and have been associated with GI adverse events. Thus, current dosing guidelines recommend that the patient not eat or lie down for...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(03)90005-1
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Inhaled dry powder insulin (IDPI) is the first inhaled insulin approved for the treatment of type 1 and type 2 diabetes mellitus (DM). OBJECTIVE:This article reviews available information on IDPI, focusing on its clinical pharmacokinetics, comparative efficacy, tolerability, adverse events, dosage and admin...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2007.05.015
更新日期:2007-05-01 00:00:00
abstract::The management of patients with congestive heart failure (CHF) can place a significant economic burden on managed care organizations, leading providers to seek treatments that are cost-effective. Diuretics play a significant role in the treatment of edema associated with CHF. We evaluated the use of 2 loop diuretics, ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/s0149-2918(99)80007-1
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND:Systemic absorption of topical fluorouracil, although usually low, may vary as a result of the specific skin disease, product formulation, and other factors. OBJECTIVE:The present study was conducted to determine the pharmacokinetic profile and tolerability of a new topical 0.5% fluorouracil cream formulati...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0149-2918(01)80078-3
更新日期:2001-06-01 00:00:00
abstract:PURPOSE:Methylphenidate hydrochloride extended-release chewable tablet (MPH ERCT) is approved for treatment of attention deficit hyperactivity disorder in patients aged 6 years and older. This article evaluates the pharmacokinetic parameters and relative bioavailability of MPH ERCT when chewed versus swallowed whole. ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2018.03.016
更新日期:2018-05-01 00:00:00
abstract::The subjects were 20 chronic schizophrenic patients with dyslipidemia (total cholesterol levels greater than or equal to 220 mg/dl, triglycerides greater than or equal to 150 mg/dl, or high-density lipoprotein cholesterol less than or equal to 40 mg/dl) who had been receiving neuroleptics for a mean of ten years. Each...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::Patient counseling is an important aspect of family planning. Patient choice, compliance, and satisfaction with a contraceptive method depend heavily on the counseling experience. This is especially true in the United Kingdom where contraceptives are provided to patients at no direct cost to them. Women are therefore ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(96)80187-1
更新日期:1996-01-01 00:00:00
abstract::Lyme disease produces a diverse clinical picture that can include serious and potentially debilitating cardiac, neurologic, joint, and skin involvement. It is characterized in three stages--early localized (stage I), early disseminated (stage II), and late disseminated (stage III)--and medical management is highly dep...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(98)80081-7
更新日期:1998-09-01 00:00:00
abstract::Pediatric patients experience unique differences from the adult population in pharmacokinetic parameters and, consequently, require individualized dosing. Medications useful in pediatric medicine often lack a therapeutic indication and dosing guideline for this population. In addition, the absence of an available pedi...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1991-09-01 00:00:00
abstract:BACKGROUND:Eperisone hydrochloride, a centrally acting muscle relaxant, is a calcium antagonist that causes vasodilation and antispastic actions. Aceclofenac, an anti-inflammatory analgesic and antipyretic drug, has similar efficacy and improved gastrointestinal tolerance compared with other nonsteroidal anti-inflammat...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2013.08.012
更新日期:2013-10-01 00:00:00
abstract:PURPOSE:The goal of this study was to assess and compare the potential clinical and economic value of emerging bone-forming agents using the only currently available agent, teriparatide, as a reference case in patients at high, near-term (imminent, 1- to 2-year) risk of osteoporotic fractures, extending to a lifetime h...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.05.348
更新日期:2017-07-01 00:00:00
abstract::A recent report of two isolates of Streptococcus bovis resistant to killing by low levels of penicillin G prompted this study of the in vitro susceptibility of 100 clinical isolates of S bovis to six antibiotics. Using a microdilution method, we found the minimum bactericidal concentrations for 99% of the isolates to ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::One hundred fourteen women undergoing vaginal hysterectomy (n = 63) or abdominal hysterectomy (n = 51) were randomly allocated to one of three groups: regimen 1--cefotaxime perioperatively; regimen 2--cefotaxime perioperatively and for 24 hours postoperatively; or regimen 3--cefazolin perioperatively and for 24 hours ...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1982-01-01 00:00:00
abstract:BACKGROUND:Due to the emergence of community-associated strains, the prevalence of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections has increased substantially in pediatric patients. A vancomycin AUC(0-24)/MIC index >400 best predicts treatment outcomes for invasive MRSA infection in adults. Data ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2010.03.005
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND:Treatment of infections caused by gram-negative bacilli is increasingly challenging because of emerging resistance. Current surveillance data are informative, but may not discern differences by infection site and clinical setting, and do not incorporate pharmacodynamic (PD) characteristics when determining s...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1016/j.clinthera.2009.11.021
更新日期:2009-11-01 00:00:00
abstract::The aim of this study was to evaluate the short-term and long-term effects of felodipine, a new dihydropiridine calcium antagonist, on arterial blood pressure (BP), the renin-angiotensin-aldosterone system, diuresis, natriuresis, and the atrial natriuretic factor (ANF). In 15 essential hypertensives (WHO class II) BP,...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract:OBJECTIVE:The aim of this research letter was to describe the use of N-carbamoyl-L-glutamate as first-line treatment of hyperammonemia in a 4-month-old female patient with propionic acidemia (PA). METHODS:A 4-month-old female patient weighing 3.9 kg presented with decompensation with PA and initial hyperammonemia of 4...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2010.04.004
更新日期:2010-04-01 00:00:00
abstract:PURPOSE:Surgery, radiotherapy, and chemotherapy are the mainstays of cervical cancer treatment. Many patients receive multiple treatment modalities, each with its own long-term effects. Given the high 5-year survival rate for cervical cancer patients, evaluation and improvement of long-term quality of life are essentia...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2014.11.013
更新日期:2015-01-01 00:00:00
abstract::The legal right to assert a conscientious objection is reviewed, using as an example the dispensing of abortifacient drugs by pharmacists. The three areas of law that most significantly concern the right to assert a conscientious refusal are employment law, conscience clauses, and religious discrimination law. Each of...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract:BACKGROUND:New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had progressed on sunitinib and...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2013.10.004
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:Despite increasing investigation in the area of cardiovascular instability in preterm infants, huge gaps in knowledge remain. None of the current treatments for hypotension, including the use of inotropic agents, have been well studied in the preterm population, and data regarding safety and efficacy are lac...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2006.09.006
更新日期:2006-09-01 00:00:00
abstract:BACKGROUND:Breast cancer surgery performed with the patient under general anesthesia has been associated with a relatively high incidence of postoperative nausea and vomiting (PONV). Between 60% and 80% of patients who undergo mastectomy (with axillary dissection) experience PONV. We previously reported that propofol a...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验,收录出版
doi:10.1016/j.clinthera.2008.11.011
更新日期:2008-11-01 00:00:00
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journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2020.09.006
更新日期:2020-10-01 00:00:00
abstract:PURPOSE:Each year in France, varicella and zoster affect large numbers of children and adults, resulting in medical visits, hospitalizations for varicella- and zoster-related complications, and societal costs. Disease prevention by varicella vaccination is feasible, wherein a plausible option involves replacing the com...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.01.006
更新日期:2015-04-01 00:00:00
abstract::Flumazenil is a new drug indicated for the reversal of the sedative effects of benzodiazepines mediated at the benzodiazepine-receptor site. Worldwide sources to date have disclosed 43 cases of seizures related, at least temporally, to the intravenous administration of flumazenil. There was no apparent relationship be...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1992-03-01 00:00:00
abstract:BACKGROUND:Desvenlafaxine succinate, a serotonin-norepinephrine reuptake inhibitor (SNRI), was approved by the US Food and Drug Administration (FDA) in February 2008 for the treatment of adult patients with major depressive disorder (MDD). Desvenlafaxine is the third SNRI approved by the FDA for this indication. OBJEC...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2009.07.012
更新日期:2009-06-01 00:00:00
abstract:PURPOSE:Coadministration of morphine with oral gabapentin has been shown to increase plasma gabapentin concentrations. This study evaluated whether there was any interaction between gabapentin enacarbil (GEn), which is a prodrug of gabapentin, and morphine in terms of pharmacokinetics, pharmacodynamics, safety, and tol...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.clinthera.2014.10.015
更新日期:2015-02-01 00:00:00
abstract:BACKGROUND:The US Food and Drug Administration approved pemetrexed in February 2004 for the treatment of malignant pleural mesothelioma (MPM) in combination with cisplatin in patients with unresectable disease or for whom curative surgery is not an option. Pemetrexed is the first agent approved for the treatment of MPM...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2005.09.010
更新日期:2005-09-01 00:00:00