Abstract:
PURPOSE:Our aim was to develop and validate the extrapolative performance of a regression model using a limited sampling strategy for accurate estimation of the area under the plasma concentration versus time curve for saroglitazar. METHODS:Healthy subject pharmacokinetic data from a well-powered food-effect study (fasted vs fed treatments; n = 50) was used in this work. The first 25 subjects' serial plasma concentration data up to 72 hours and corresponding AUC0-t (ie, 72 hours) from the fasting group comprised a training dataset to develop the limited sampling model. The internal datasets for prediction included the remaining 25 subjects from the fasting group and all 50 subjects from the fed condition of the same study. The external datasets included pharmacokinetic data for saroglitazar from previous single-dose clinical studies. Limited sampling models were composed of 1-, 2-, and 3-concentration-time points' correlation with AUC0-t of saroglitazar. Only models with regression coefficients (R2) >0.90 were screened for further evaluation. The best R2 model was validated for its utility based on mean prediction error, mean absolute prediction error, and root mean square error. Both correlations between predicted and observed AUC0-t of saroglitazar and verification of precision and bias using Bland-Altman plot were carried out. FINDINGS:None of the evaluated 1- and 2-concentration-time points models achieved R2 > 0.90. Among the various 3-concentration-time points models, only 4 equations passed the predefined criterion of R2 > 0.90. Limited sampling models with time points 0.5, 2, and 8 hours (R2 = 0.9323) and 0.75, 2, and 8 hours (R2 = 0.9375) were validated. Mean prediction error, mean absolute prediction error, and root mean square error were <30% (predefined criterion) and correlation (r) was at least 0.7950 for the consolidated internal and external datasets of 102 healthy subjects for the AUC0-t prediction of saroglitazar. The same models, when applied to the AUC0-t prediction of saroglitazar sulfoxide, showed mean prediction error, mean absolute prediction error, and root mean square error <30% and correlation (r) was at least 0.9339 in the same pool of healthy subjects. IMPLICATIONS:A 3-concentration-time points limited sampling model predicts the exposure of saroglitazar (ie, AUC0-t) within predefined acceptable bias and imprecision limit. Same model was also used to predict AUC0-∞. The same limited sampling model was found to predict the exposure of saroglitazar sulfoxide within predefined criteria. This model can find utility during late-phase clinical development of saroglitazar in the patient population.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Joshi SN,Srinivas NR,Parmar DVdoi
10.1016/j.clinthera.2018.01.016subject
Has Abstractpub_date
2018-03-01 00:00:00pages
456-468.e1issue
3eissn
0149-2918issn
1879-114Xpii
S0149-2918(18)30049-3journal_volume
40pub_type
杂志文章,随机对照试验abstract::The monomeric insulin analogue insulin lispro (Lys B28, Pro B29) is a rapid-acting insulin with a shorter duration of activity than human regular insulin. This compound has the advantage of reducing early postprandial hyperglycemia and the accompanying late hypoglycemia, thereby improving overall blood glucose control...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(98)80040-4
更新日期:1998-01-01 00:00:00
abstract::Self-care with over-the-counter (OTC) medicines has evolved from the "dark ages" of patent medicine manufacture and sale to a modern era of new drug development involving prescription-to-OTC switch. This evolution is largely due to the OTC Review, which placed science at the cornerstone of safety, effectiveness, and l...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(98)80018-0
更新日期:1998-01-01 00:00:00
abstract::A single 5-gm dose of mezlocillin or a placebo was administered intravenously 30 minutes before surgery to patients undergoing emergency cesarean section. The assignment of drug or placebo was randomized. Postoperative morbidity occurred in 62.5% of patients receiving placebo and in 18.4% of those receiving mezlocilli...
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:1985-01-01 00:00:00
abstract:BACKGROUND:The therapeutic effectiveness of Echinacea in the treatment and the prevention of colds has been debated. Studies of naturally occurring colds are hampered by variability in time from onset of symptoms to treatment and by heterogeneity in trial design. Experimental infection studies allow for the standardiza...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.clinthera.2006.02.001
更新日期:2006-02-01 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::A four-week crossover study to compare the efficacy of an acne cleanser containing 2% salicylic acid with that of a 10% benzoyl peroxide wash was conducted in 30 patients with acne vulgaris. The results demonstrated that only patients treated with the salicylic acid cleanser had a significant reduction in comedones. P...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1989-03-01 00:00:00
abstract::Fifty clinic patients with mild to moderately severe dermatoses were treated for three weeks with bufexamac, a hydroxamic acid compound with anti-inflammatory properties. Half the patients had either contact or seborrheic dermatitis; the remaining 25 were distributed among five other diagnostic categories. Evaluation ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00
abstract:OBJECTIVE:This study describes patients' and physicians' perceptions of issues related to dosing adherence with topical therapies for lowering intraocular pressure before and after use of the travoprost dosing aid (Travatan Dosing Aid, Alcon Research Ltd., Fort Worth, Texas). METHODS:The study had an open-label, multi...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1016/j.clinthera.2006.11.001
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND:Trials of monotherapy with alpha(1)-adrenergic-receptor antagonists (alpha(1)ARAs) and 5 alpha-reductase inhibitors (5ARIs) have found that the former drug class is effective in managing benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) and improving the maximal urinary flow rate...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(07)80077-4
更新日期:2007-03-01 00:00:00
abstract::Despite the fact that reflux esophagitis is a multifactorial disease, inhibition of gastric acid secretion is the mainstay of medical treatment, both for moderate and severe cases. Antisecretory agents lower the acidity of the refluxate, thus decreasing its aggressive effect, which favors the mucosal healing process. ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1993-01-01 00:00:00
abstract:PURPOSE:This study aims to investigate glycosylated hemoglobin (HbA1c), between-laboratory imprecision (%CV), and pass rates from 2012 to 2015 in Nanjing to provide evidence for improving the HbA1c measurement. METHODS:This was a retrospective, descriptive analysis of HbA1c levels obtained from participating hospitals...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.11.013
更新日期:2017-01-01 00:00:00
abstract::This commentary reviews the difficulties in formulating oral products for children. The significance of the fragmentation of the pediatric population in terms of development and ability to ingest different dosage formulations is examined. It is postulated that a flexible formulation, acceptable by all patient groups, ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2014.01.010
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:Bisphosphonates are the class of medication used most widely to treat osteoporosis. Since an article reported that patients who used zoledronic acid, a bisphosphonate, had a higher proportion of atrial fibrillation (AF) in 2007, the issue of bisphosphonates and AF has become a growing concern. Due to the wid...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.07.012
更新日期:2011-09-01 00:00:00
abstract::In trying to identify the therapeutic impact of a drug, clinical trials eliminate potentially confounding factors such as comorbidities, poor compliance and treatment errors in diagnosis, dosing, and drug interactions. Elimination of these variables means that attempts to use clinical data as the basis for predicting ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/0149-2918(95)80098-0
更新日期:1995-11-01 00:00:00
abstract:INTRODUCTION:Acute generalized exanthematous pustulosis (AGEP) is a clinical reaction pattern that is principally drug induced and is characterized by acute, extensive formation of nonfollicular sterile pustules on an erythematous and edematous substrate. Hydroxychloroquine (HHCQ), an antimalarial drug widely used to t...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2008.05.014
更新日期:2008-05-01 00:00:00
abstract::A drug surveillance study was performed to determine the tolerance and safety of quinapril in the treatment of patients with stage 1 or 2 hypertension. The trial was noncomparative, open-label, uncontrolled, and nonrandomized. Patients with secondary hypertension, heart failure, other heart diseases, and other serious...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/s0149-2918(96)80046-4
更新日期:1996-09-01 00:00:00
abstract:PURPOSE:The objective of this study was to evaluate the efficacy and tolerability of a triple combination of amlodipine/losartan/rosuvastatin in patients with hypertension and hypercholesterolemia. METHODS:A randomized, multicenter, double-blind, placebo-controlled study was conducted. Eligible patients with hypertens...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2017.10.013
更新日期:2017-12-01 00:00:00
abstract::As policy makers explore ways to reform the Medicare system, the inevitable question of prescription drug coverage for the elderly will surface. This is an opportunity to revisit and balance the attractiveness of including a prescription benefit against the fear of increases in expenditures. Prudent examination of the...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(97)80016-1
更新日期:1997-11-01 00:00:00
abstract:BACKGROUND:Cobalamin (vitamin B12) deficiency, the most common cause of megaloblastic anemia, is treated with intramuscular (IM) cobalamin. It has been suggested by some investigators that oral (p.o.) cobalamin treatment may be as effective in the treatment of this condition, with the advantages of ease of administrati...
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(03)90096-8
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND:Alendronate, an oral bisphosphonate, is available for the treatment of osteoporosis in a 70-mg once-weekly and a 10-mg once-daily formulation. OBJECTIVES:This study aimed to determine patient preference for once-weekly versus once-daily dosing with alendronate, and to determine which treatment regimen the p...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(02)80085-6
更新日期:2002-11-01 00:00:00
abstract:BACKGROUND:Glucagon-like peptide (GLP-1) is a neuroendocrine hormone that increases blood glucose and is a drug target for treatment of type 2 diabetes. Liraglutide, a subcutaneous, once-daily GLP-1 agonist, is approved for the treatment of type 2 diabetes in the United States and Europe. It also has been studied for w...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2011.06.004
更新日期:2011-07-01 00:00:00
abstract:PURPOSE:This observational study of oncologic clinical practices was designed to describe real-world patterns of use of emerging therapies (abiraterone acetate, cabazitaxel, enzalutamide, radium-223, sipuleucel-T) in patients with castration-resistant prostate cancer and to characterize their concomitant use with denos...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2017.12.015
更新日期:2018-04-01 00:00:00
abstract:PURPOSE:The information that is available when marketing authorizations are approved is limited. Pharmacovigilance has an important role during the postauthorization period, and alerts published by national authorities allow health care professionals to be informed about new data on safety profiles. This study therefor...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.07.015
更新日期:2015-09-01 00:00:00
abstract::This study categorizes the types of inappropriate intravenous prescriptions in hospitalized patients in China. Prescription data from 2016 were retrospectively analyzed based on predefined categories of inappropriateness. Of the 123,521 patients included, 89.2% received intravenous medications, contributing to 80% of ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2019.05.009
更新日期:2019-08-01 00:00:00
abstract:PURPOSE:Huoxue-Tongluo lyophilized powder for injection (HTLPI), a traditional Chinese medicine preparation, is a compound of Persicae semen and Paeoniae Radix Rubra that is used mainly for treating blood-stasis obstruction syndrome in the acute stage of cerebral ischemic stroke. Amygdalin (AD) and paeoniflorin (PF) ar...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2015.12.005
更新日期:2016-02-01 00:00:00
abstract:PURPOSE:The effects of air pollutants have been receiving increased attention both clinically and in the media. One such pollutant is mold, fungal growth in the form of multicellular filaments known as hyphae. The growth of molds is omnipresent not only in outdoor settings but also in indoor environments containing exc...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2018.05.004
更新日期:2018-06-01 00:00:00
abstract:BACKGROUND:Many active pharmaceutical ingredients taste bitter and thus are aversive to children as well as many adults. Encapsulation of the medicine in pill or tablet form, an effective method for adults to avoid the unpleasant taste, is problematic for children. Many children cannot or will not swallow solid dose fo...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2013.06.007
更新日期:2013-08-01 00:00:00
abstract:PURPOSE:Selection and prompt initiation of the appropriate empiric antimicrobial therapy are critical to decrease morbidity and mortality and shorten the length of hospitalization among patients with hospital-associated intra-abdominal infections (HA-IAIs). Therapeutic choices for the treatment of patients with HA-IAI ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2016.04.035
更新日期:2016-06-01 00:00:00
abstract::Steady-state bioavailability of a sustained-release quinidine gluconate formulation was compared with that of a sustained-release quinidine sulfate preparation in a crossover study. Sixteen healthy men were given multiple doses (two tablets every 12 hours) of the two drugs in randomized sequence. Blood samples were ob...
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:1983-01-01 00:00:00
abstract:OBJECTIVE:This study was designed to assess the efficacy and safety of glimepiride plus rosiglitazone for type 2 diabetes mellitus (DM) inadequately controlled with rosiglitazone monotherapy. METHODS:This was a randomized, double-blind, placebo-controlled, multicenter study Patients were assigned to a 6-week forced ti...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:2004-11-01 00:00:00