A Systematic Review and Empirical Analysis of the Relation Between Dose and Duration of Drug Action

Hughes, Dyfrig; Aronson, Jeffrey K

doi:10.1177/0091270008329555

Cited by 7 publications

(4 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Age and gender, are two other significant factors which influence the pharmacokinetics and pharmacodynamics of a drug [104,105]. Hughes and Aronson [106] defined that duration of action of a drug is directly proportional to the logarithm of dose for a wide range of different drugs, revealing the significant role played by both these variables on the treatment outcomes. Therefore, when drugs are administrated, a meticulous understanding of the dose–response relationship is of great significance for achieving the specific therapeutic effect while minimizing their side-effects [107,108].…”

Section: Introductionmentioning

confidence: 99%

Advancing stem cell therapy from bench to bedside: lessons from drug therapies

2014

View full text Add to dashboard Cite

The inadequacy of existing therapeutic tools together with the paucity of organ donors have always led medical researchers to innovate the current treatment methods or to discover new ways to cure disease. Emergence of cell-based therapies has provided a new framework through which it has given the human world a new hope. Though relatively a new concept, the pace of advancement clearly reveals the significant role that stem cells will ultimately play in the near future. However, there are numerous uncertainties that are prevailing against the present setting of clinical trials related to stem cells: like the best route of cell administration, appropriate dosage, duration and several other applications. A better knowledge of these factors can substantially improve the effectiveness of disease cure or organ repair using this latest therapeutic tool. From a certain perspective, it could be argued that by considering certain proven clinical concepts and experience from synthetic drug system, we could improve the overall efficacy of cell-based therapies. In the past, studies on synthetic drug therapies and their clinical trials have shown that all the aforementioned factors have critical ascendancy over its therapeutic outcomes. Therefore, based on the knowledge gained from synthetic drug delivery systems, we hypothesize that by employing many of the clinical approaches from synthetic drug therapies to this new regenerative therapeutic tool, the efficacy of stem cell-based therapies can also be improved.

show abstract

Section: Introductionmentioning

confidence: 99%

Advancing stem cell therapy from bench to bedside: lessons from drug therapies

2014

View full text Add to dashboard Cite

show abstract

“…The duration of the neuromuscular block depends on the choice and dose of NMBA administered. We found an approximately log‐linear correlation between the amount of NMBA administered and the duration of spontaneous recovery 117 …”

Section: Discussionmentioning

confidence: 70%

“…We found an approximately loglinear correlation between the amount of NMBA administered and the duration of spontaneous recovery. 117 Overall, an approximately negative log-linear relationship between age and duration of NMBA effect could be demonstrated.…”

Section: Discussionmentioning

confidence: 84%

Spontaneous recovery from neuromuscular block after a single dose of a muscle relaxant in pediatric patients: A systematic review using a network meta‐analytic and meta‐regression approach

Vanlinthout,

Driessen,

Stolker

et al. 2024

Pediatric Anesthesia

View full text Add to dashboard Cite

BackgroundAge‐related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put pediatric patients at risk of postoperative residual curarization (PORC). To date, the duration of neuromuscular blocking agent effect in children has not been analyzed in a quantitative review. The current meta‐analysis aimed to compare spontaneous recovery following administration of various types and doses of neuromuscular blocking agents and to quantify the effect of prognostic variables associated with the recovery time in pediatric patients.MethodWe searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25–75), and to ≥90% train‐of‐four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25‐75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random‐effects network and pairwise meta‐analyses along with meta‐regression were used to evaluate the results.ResultsWe used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta‐analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25‐75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log‐linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2–11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d–12 M), respectively. We found a negative log‐linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance.ConclusionsThe times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent.

show abstract

“…For example, in a survey of all issues of four pharmacology journals published between January 1980 and October 2005 (more than 18,000 articles in 189 volumes), only 33 articles reported pharmacodynamic response versus time curves for four or more different doses. 3 Given the dearth of primary studies reporting dose–response relationships in humans, we consider here how such relationships can be derived through secondary analyses (meta-analyses) of multiple trials.…”

Section: Introductionmentioning

confidence: 99%

Methods for meta-analysis of pharmacodynamic dose–response data with application to multi-arm studies of alogliptin

Langford

Aronson

Valkenhoef

et al. 2016

Stat Methods Med Res

View full text Add to dashboard Cite

Standard methods for meta-analysis of dose-response data in epidemiology assume a model with a single scalar parameter, such as log-linear relationships between exposure and outcome; such models are implicitly unbounded. In contrast, in pharmacology, multi-parameter models, such as the widely used E model, are used to describe relationships that are bounded above and below. We propose methods for estimating the parameters of a dose-response model by meta-analysis of summary data from the results of randomized controlled trials of a drug, in which each trial uses multiple doses of the drug of interest (possibly including dose 0 or placebo). We assume that, for each randomized arm of each trial, the mean and standard error of a continuous response measure and the corresponding allocated dose are available. We consider weighted least squares fitting of the model to the mean and dose pairs from all arms of all studies, and a two-stage procedure in which scalar inverse-variance meta-analysis is performed at each dose, and the dose-response model is fitted to the results by weighted least squares. We then compare these with two further methods inspired by network meta-analysis that fit the model to the contrasts between doses. We illustrate the methods by estimating the parameters of the E model to a collection of multi-arm, multiple-dose, randomized controlled trials of alogliptin, a drug for the management of diabetes mellitus, and further examine the properties of the four methods with sensitivity analyses and a simulation study. We find that all four methods produce broadly comparable point estimates for the parameters of most interest, but a single-stage method based on contrasts between doses produces the most appropriate confidence intervals. Although simpler methods may have pragmatic advantages, such as the use of standard software for scalar meta-analysis, more sophisticated methods are nevertheless preferable for their advantages in estimation.

show abstract

A Systematic Review and Empirical Analysis of the Relation Between Dose and Duration of Drug Action

Cited by 7 publications

References 45 publications

Advancing stem cell therapy from bench to bedside: lessons from drug therapies

Advancing stem cell therapy from bench to bedside: lessons from drug therapies

Spontaneous recovery from neuromuscular block after a single dose of a muscle relaxant in pediatric patients: A systematic review using a network meta‐analytic and meta‐regression approach

Methods for meta-analysis of pharmacodynamic dose–response data with application to multi-arm studies of alogliptin

Contact Info

Product

Resources

About