Pharmacokinetics and Pharmacodynamics of Cisatracurium in Young and Elderly Adult Patients

1996 ◽  
Vol 84 (5) ◽  
pp. 1083-1091 ◽  
Author(s):  
Shahpoor S. Sorooshian ◽  
Michael A. Stafford ◽  
Nigel B. Eastwood ◽  
Alastair H. Boyd ◽  
Christopher J. Hull ◽  
...  
Keyword(s):  
Muscle Relaxant ◽  
Time Course ◽  
Venous Blood ◽  
The Elderly ◽  
Adult Patients ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Elderly Adult ◽  
Elderly Adults ◽  
Duration Of Action

Background The effects of a muscle relaxant may differ in elderly compared with young adult patients for a variety of reasons. The authors compared the effects of a new muscle relaxant (cisatracurium) in young and elderly adults and used pharmacokinetic/pharmacodynamic modeling to identify factors explaining differences in time course of effect. Methods Thirty-one young (18-50 yr) and 33 elderly ( > 65 yr) patients anesthetized with nitrous oxide, isoflurane, and fetanyl were studied. Cisatracurium (0.1 mg/kg) was given after induction of anesthesia and later additional boluses of 0.025 mg/kg or an infusion of cisatracurium was given. Neuromuscular transmission was measured using the first twitch of the train-of-four response at the adductor pollicis after supramaximal stimulation of the ulnar nerve at 2 Hz every 15 s. Five venous blood samples were obtained for plasma drug concentration at intervals ranging from 2 to 120 min from every patient. Three additional samples were obtained from those who received an infusion. A population pharmacokinetic/pharmacodynamic model was fitted to the plasma concentration and effect data. The parameters of the model were permitted to vary with age to identify where differences existed between young and elderly adults. Results Onset of block was delayed in the elderly; values being mean 3.0 (95% confidence interval 1.75-11.4) min and 4.0 (2.4-6.5) min in the young and elderly, respectively (P < 0.01). Duration of action was similar in the two groups. Plasma clearance was 319 (293-345) ml/min in the study population and did not differ between young and elderly patients. Apparent volume of distribution was 13.28 (9.9-16.7) 1 and 9.6 (7.6-11.7) 1 in the elderly and young adults, respectively (P < 0.05). There also were differences in pharmacodynamic parameters between the young and elderly; the predominant change being a slower rate of biophase equilibration (ke0) in the elderly (0.060 [0.052-0.068])/min compared with the young (0.071 [0.065-0.077]/min; P < 0.05). Conclusions The pharmacokinetics of cisatracurium differ only marginally between young and elderly adults. Onset is delayed in the elderly because of slower biophase equilibration.

scholarly journals Sexuality in Elderly Adults: Study on Knowledge and Attitudes Related to Sexuality in Older Adults

2019 ◽  
Vol 11 (7) ◽  
pp. 184
Author(s):  
Saldarriaga G. Guillermina ◽  
Ruydiaz G. Keydis ◽  
Jiménez A. Sindy ◽  
Fernández A. Shirley
Keyword(s):  
Older Adults ◽  
The Elderly ◽  
Attitude Scale ◽  
Natural Phenomenon ◽  
Elderly Adult ◽  
Elderly Adults ◽  
Cross Sectional ◽  
Knowledge And Attitudes ◽  
Inadequate Knowledge ◽  
Level Of Knowledge

INTRODUCTION: Aging is a universal and natural phenomenon that causes structural and physiological changes. It is a process of deterioration, progressive and intrinsic. OBJECTIVE: Determining the level of knowledge and attitudes about sexuality in older adults living in three centers. MATERIALS & METHODS: A cross- sectional descriptive study in 80 elderly adults enrolled and attending three life centers on the City of Cartagena, Questionnaires about Knowledge on Sexual Health of the Elderly (2007) and the Attitude Scale towards Sexuality were applied in the Elderly Adult (Scale ACASAM-MM-2013). RESULTS: On a population of elderly adults, female sex predominated 58%, average age of 74 years, adults widowers 35% of the total population, and 31% maintain a relationship. Older adults reported having inadequate knowledge in relation to the three sessions evaluated, the access section to a couple predominated, they reflected having an average general attitude, being the cognitive and volitional component those of greater significance. CONCLUSION: The attitudes that reflect the elderly is favorable, being so, that the elderly are clear that society notice them regarding sexuality, and are autonomous to express and experience it.

scholarly journals Pharmacogenomics of methadone: a narrative review of the literature

2020 ◽  
Vol 21 (12) ◽  
pp. 871-887
Author(s):  
Senthil Packiasabapathy ◽  
Blessed W Aruldhas ◽  
Nicole Horn ◽  
Brian R Overholser ◽  
Sara K Quinney ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Single Gene ◽  
Predictive Ability ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Cytochrome P450 Enzymes ◽  
Duration Of Action ◽  
P Glycoprotein ◽  
Surgical Pain ◽  
Clinical Responses

Background: Methadone, a synthetic opioid with longer duration of action and lower abuse potential compared with morphine, is used to prevent opioid withdrawal, as well as to manage chronic and acute surgical pain. The variability in response to methadone has been widely recognized. The purpose of this article is to review the literature on the pharmacogenetic factors underlying this variability. Materials & methods: This is a narrative overview of the literature on the genetic variants affecting pharmacodynamics and pharmacokinetics of methadone, retrieved from searches of databases such as PubMed and google scholar. Discussion: Clinical responses to methadone may be affected by genetic variants in the opioidergic, dopaminergic and neurotrophic pathways. Polymorphisms in genes related to disposition and elimination of methadone alter the pharmacokinetics, and possibly pharmacodynamics of methadone. Cytochrome P450 enzymes and P-glycoprotein variants contribute to the interindividual variability in methadone pharmacokinetics. Evidence for single gene variants affecting methadone response remains weak. Multiple genetic variants must be considered in conjunction to improve predictive ability. Conclusion: Evidence remains scarce at this time, to recommend pharmacogenetic testing before methadone administration. Well-powered clinical studies are needed with population pharmacokinetic-pharmacodynamic modeling and multigenetic signature-based predictions to enable tailored use of methadone in clinical practice.

scholarly journals Population Pharmacokinetic–Pharmacodynamic Modeling of Epidural Anesthesia

2008 ◽  
Vol 109 (4) ◽  
pp. 664-674 ◽  
Author(s):  
Erik Olofsen ◽  
Antonius G. L. Burm ◽  
Mischa J. G. Simon ◽  
Bernadette Th. Veering ◽  
Jack W. van Kleef ◽  
...  
Keyword(s):  
Epidural Anesthesia ◽  
Local Anesthetics ◽  
Time Course ◽  
Pharmacodynamic Model ◽  
Pharmacodynamic Modeling ◽  
Effect Compartment ◽  
Population Pharmacokinetic ◽  
Concentration Data ◽  
Sensory Blockade ◽  
Analgesic Effects

Background In previous studies, the authors reported on the absorption and disposition kinetics of levobupivacaine and ropivacaine. The current study was designed to develop a population pharmacokinetic-pharmacodynamic model capable of linking the kinetic data to the analgesic effects of these local anesthetics (i.e., sensory neural blockade). Methods A disposition compartmental model was fitted to concentration data of the intravenously administered deuterium-labeled anesthetics, and a model consisting of two parallel absorption compartments and the identified disposition compartments was fitted to concentration data of the concomitantly epidurally administered unlabeled anesthetics. The epidural segments were modeled by individual central and peripheral absorption compartments and effect sites, which were fitted to the simultaneously acquired pinprick data. A covariate model incorporated the effects of age. Results The threshold for epidural anesthesia increased from the lower to the higher segments. The central effect compartment equilibration half-lives were approximately 15 min for levobupivacaine and 25 min for ropivacaine. For levobupivacaine, age reduced the equilibration half-lives at all segments; for ropivacaine, age increased the anesthetic sensitivity at segments T12 and higher. Conclusions A population pharmacokinetic-pharmacodynamic model was developed that quantitatively described sensory blockade during epidural anesthesia, including the effects of age. The model may be useful to individualize dose requirements, to predict the time course of sensory blockade, and to study new local anesthetics.

Population pharmacokinetic/pharmacodynamic modeling for the time course of tumor shrinkage by motesanib in thyroid cancer patients

2010 ◽  
Vol 66 (6) ◽  
pp. 1151-1158 ◽  
Author(s):  
Jian-Feng Lu ◽  
Laurent Claret ◽  
Liviawati Sutjandra ◽  
Mita Kuchimanchi ◽  
Rebeca Melara ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Patients ◽  
Time Course ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Tumor Shrinkage

scholarly journals Letter to the Editor: Microbiota in the Respiratory System—A Possible Explanation to Age and Sex Variability in Susceptibility to SARS-CoV-2

2021 ◽  
Vol 14 ◽  
pp. 117863612098860
Author(s):  
Vishal Shah
Keyword(s):  
Respiratory System ◽  
Elderly Population ◽  
Age Groups ◽  
The Elderly ◽  
Elderly Adult ◽  
Human Respiratory Tract ◽  
System A ◽  
Number Of Patients ◽  
Children And Young Adults ◽  
Age And Sex

The Human respiratory tract is colonized by a variety of microbes and the microbiota change as we age. In this perspective, literature support is presented for the hypothesis that the respiratory system microbiota could explain the differential age and sex breakdown amongst COVID-19 patients. The number of patients in the older and elderly adult group is higher than the other age groups. The perspective presents the possibility that certain genera of bacteria present in the respiratory system microbiota in children and young adults could be directly or through eliciting an immune response from the host, prevent full-fledged infection of SARS-CoV-2. The possibility also exists that the microbiota in older adults and the elderly population have bacteria that make it easier for the virus to cause infection. I call upon the scientific community to investigate the link between human microbiota and SARS-CoV-2 susceptibility to further understand the viral pathogenesis.

Population pharmacokinetic and pharmacodynamic modeling of epinephrine administered using a mobile inhaler

2015 ◽  
Vol 30 (6) ◽  
pp. 391-399 ◽  
Author(s):  
Sebastian Frechen ◽  
Ahmed Abbas Suleiman ◽  
Ali Mohammad Nejad Sigaroudi ◽  
Bertil Wachall ◽  
Uwe Fuhr
Keyword(s):  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic

scholarly journals Pregnancy-Related Effects on Nelfinavir-M8 Pharmacokinetics: a Population Study with 133 Women

2006 ◽  
Vol 50 (6) ◽  
pp. 2079-2086 ◽  
Author(s):  
Déborah Hirt ◽  
Jean-Marc Treluyer ◽  
Vincent Jullien ◽  
Ghislaine Firtion ◽  
Hélène Chappuy ◽  
...  
Keyword(s):  
Population Study ◽  
Time Course ◽  
Plasma Concentrations ◽  
Elimination Rate ◽  
Concomitant Administration ◽  
Individual Characteristics ◽  
Individual Treatment ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Linear Absorption

ABSTRACT A relationship between nelfinavir antiretroviral efficacy and plasma concentrations has been previously established. As physiological changes associated with pregnancy have a large impact on the pharmacokinetics of many drugs, a nelfinavir population study with women was developed, and the large intersubject variability was analyzed in order to optimize individual treatment schedules for this drug during pregnancy. A population pharmacokinetic model was developed in order to describe the concentration time course of nelfinavir and its metabolite M8 in pregnant and nonpregnant women. Individual characteristics, such as age, body weight, and weeks of gestation or delivery, which may influence nelfinavir-M8 pharmacokinetics were investigated. Data from therapeutic drug monitoring in 133 women treated with nelfinavir were retrospectively analyzed with NONMEM. Nelfinavir pharmacokinetics was described by a one-compartment model with linear absorption and elimination and M8 produced from the nelfinavir central compartment. Mean pharmacokinetic estimates and the corresponding intersubject percent variabilities for a nonpregnant woman were the following: absorption rate, 0.83 h−1; absorption lag time, 0.85 h; apparent nelfinavir elimination clearance (CL10/F), 35.5 liters/h (50%); apparent volume of distribution (V/F), 596 liters (118%); apparent formation clearance to M8 (CL1M/F), 0.65 liters/h (69%); and M8 elimination rate constant (k M0), 3.3 h−1 (59%). During pregnancy, we observed significant increases in nelfinavir (44.4 liters/h) and M8 (5 h−1) elimination but unchanged nelfinavir transformation clearance to M8, suggesting an induction of CYP3A4 but no effect on CYP2C19. Apparent nelfinavir clearance and volume showed a twofold increase on the day of delivery, suggesting a decrease in bioavailability on this day. The M8 elimination rate was increased by concomitant administration of nonnucleoside reverse transcriptase inhibitors. A trough nelfinavir plasma concentration above 1 mg/liter was previously shown to improve the antiretroviral response. The Bayesian individual pharmacokinetic estimates suggested that the dosage should not be changed in pregnant women but may be doubled on the day of delivery.

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