Pharmacokinetic and pharmacodynamic analysis of fluorouracil during 72-hour continuous infusion with and without dipyridamole.

1991 ◽  
Vol 9 (11) ◽  
pp. 2027-2035 ◽  
Author(s):  
D L Trump ◽  
M J Egorin ◽  
A Forrest ◽  
J K Willson ◽  
S Remick ◽  
...  
Keyword(s):  
Steady State ◽  
Coefficient Of Variation ◽  
Phase I Trial ◽  
Hill Equation ◽  
Percentage Reduction ◽  
Percentage Frequency ◽  
Significant Relationships ◽  
Pharmacodynamic Analysis ◽  
Steady State Plasma Concentration ◽  
The Relationship

During a phase I trial of 3-day simultaneous continuous intravenous infusions of varying doses of fluorouracil (5FUra) and 7.7 mg/kg/d of dipyridamole, we examined the relationships between 5FUra dose and steady-state plasma concentration (Css) and the percentage reduction in WBCs, as well as the percentage frequency of stomatitis. The 5FUra was administered at doses ranging from 185 mg/m2/d times three to 3,600 mg/m2/d times three. In 42 patients, 86 cycles of 5FUra plus dipyridamole and 28 cycles of 5FUra alone were analyzed. The Css of 5FUra varied even within the same dose level. When patients receiving the same 5FUra dose were considered, the interpatient coefficient of variation of 5FUra Css in cycles of 5FUra plus dipyridamole was 23% +/- 4.2%. For courses of 5FUra alone, the coefficient of variation of 5FUra was 15.6% +/- 6.5%. When the occurrence of any degree of stomatitis was related to the Css 5FUra, with patients grouped in cohorts of 2-mumol/L increments, the following equations accurately described the frequency of stomatitis: for 5FUra plus dipyridamole, percentage frequency of stomatitis = 100(1-e-0.114Css), r2 = 0.88; for 5FUra alone, percentage frequency stomatitis = 100(1-e0.122Css), r2 = 0.80. When 5FUra dose was substituted for Css, these relationships were as follows: percentage frequency of stomatitis = 100(1-e-0.00031 [dose]), r2 = 0.85; and percentage frequency of stomatitis = 100(1-e-0.00051 [dose]), r2 = 0.80. When the relationship between the percentage reduction in WBC and Css 5FUra was examined, statistically significant relationships were also apparent: for 5FUra plus dipyridamole, percentage reduction in WBC = 100(1-e-0.085Css), r2 = 0.46; for 5FUra alone, percentage reduction in WBC = 100(1-e-0.060Css), r2 = 0.61. When 5FUra dose was substituted for Css, these relatinships were as follows: percentage reduction in WBC = 100(1-e-0.00023 [dose]), r2 = 0.40; percentage reduction in WBC = 100(1-e-0.00024 [dose]), r2 = 0.65. The relationship between either Css 5FUra or dose 5FUra and either stomatitis or myelosuppression were also well described by the modified Hill equation (J Theor Biol 20:171-201, 1968). These analyses indicate that it should be possible to develop therapeutic regimens wherein 5FUra is administered to achieve a targeted Css determined by the risk and severity of toxicity deemed acceptable.

Pharmacokinetics and Pharmacodynamics of Imatinib in a Phase I Trial With Chronic Myeloid Leukemia Patients

2004 ◽  
Vol 22 (5) ◽  
pp. 935-942 ◽  
Author(s):  
Bin Peng ◽  
Michael Hayes ◽  
Debra Resta ◽  
Amy Racine-Poon ◽  
Brian J. Druker ◽  
...  
Keyword(s):  
Steady State ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Phase I Trial ◽  
Drug Exposure ◽  
Dose Range ◽  
Once Daily ◽  
Concentration Time ◽  
The Relationship ◽  
Dose Proportional

Purpose To evaluate the basic pharmacokinetic (PK) characteristics of imatinib mesylate and assess the relationship between the PK and pharmacodynamic (PD) properties of the drug. Patients and Methods The PK and PD properties of imatinib were investigated during a phase I trial that included 64 adult patients with Philadelphia chromosome–positive leukemias. Patients received imatinib orally once or twice daily. PK parameters of imatinib, derived from the plasma concentration–time curves, were determined. PD response, defined as the WBC after 1 month of treatment with imatinib, was used to develop an efficacy model. A maximum inhibition–effect model was used to describe the relationship between reduction in WBC and drug exposure parameters. Results Imatinib exposure was dose proportional after oral administration for the dose range of 25 to 1,000 mg. There was a 1.5- to three-fold drug accumulation after repeated once-daily dosing. Mean plasma trough concentration was 0.57 μg/mL (approximately 1 μmol/L) 24 hours after administration of 350 mg of imatinib at steady-state, which exceeds the 50% inhibitory concentration required to inhibit proliferation of Bcr-Abl–positive leukemic cells. Analysis of PK/PD relationships indicates that the initial hematologic response depends on the administered dose for patients with chronic myeloid leukemia. Conclusion Drug exposure (area under the concentration-time curve) is dose proportional for the dose range of 25 to 1,000 mg, and there is a 1.5- to three-fold drug accumulation at steady-state after once-daily dosing. Analysis of the relationship between PD (WBC reduction) and PK parameters at steady-state indicates that a dose of 400 mg or greater is required for maximal PD effect.

Pharmacokinetic and pharmacodynamic analysis of fluorouracil in nasopharyngeal cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13021-e13021
Author(s):  
Liping Zhao ◽  
Wanli Liu ◽  
Chong Zhao ◽  
Xiang Guo ◽  
Yan Huang ◽  
...  
Keyword(s):  
Steady State ◽  
Nasopharyngeal Cancer ◽  
Target Range ◽  
Therapeutic Drug ◽  
Severe Toxicity ◽  
Pharmacodynamic Analysis ◽  
Treatment Naïve ◽  
Tumor Types ◽  
The Relationship ◽  
Severe Mucositis

e13021 Background: Pharmacokinetic (PK) variability of 5-FU has been demonstrated for +30 years and a significant link between 5-FU exposure and therapeutic response has been identified. A maximum tolerated exposure (MTE) using area under curve (AUC) has been characterized for various regimens and therapeutic drug management (TDM) has been used to achieve effective dosing in several tumor types. The regimen most used to treat nasopharyngeal cancer (NPC) is cisplatin and 5-FU. The objective of this study was to characterize the PK variability of 5-FU in this population and examine the relationship between AUC and toxicity. The 5-FU MTE in this Chinese population will be compared with the MTE identified for HNC European patients. Methods: Fifty-three treatment naïve Chinese NPC patients were administered cisplatin (80mg/m2, day 1) and 5-FU (4g/m2, 120 h continuous infusion) and had blood samples collected at steady state after the first 18h of 5-FU infusion. Plasma was analyzed by a 5-FU immunoassay and AUC calculated from the steady state concentrations. We examined the relationship between 5-FU AUC and 5-FU-related toxicities (mucositis and myelosuppression). Results: The patient AUC values varied widely, ranging from 20 to 103 mg · h/L. 34% of the patients were within the target range of 25-35 mg· h/L , 15% were below and 51% were above the range. Toxicity was recorded for 53 patients. Severe mucositis in 17 and myelosuppression in 1 of 27 patients occurred with 5-FU exposure above the target range, versus no severe toxicity in any of the 27 patients within or below the target range (p=0.000). ROC analysis for 5-FU AUC and severe mucositis identified a cut-point of 37 mg· h/L (p<0.001). Conclusions: Results of this study demonstrate wide PK-variability of 5-FU exposure and a significant relationship between severe toxicity and AUC in Chinese NPC patients. The study confirms that the MTE in this population is similar to a European HNC population treated with cisplatin/5-FU. TDM using the target range of 25-35 mg· h/L may have benefit in lowering toxicity in NPC patients.

The Pharmacokinetics and Steady State Pharmacodynamics of Mivacurium in Children 

1998 ◽  
Vol 88 (4) ◽  
pp. 978-983 ◽  
Author(s):  
Dorothea A. Markakis ◽  
Marie Lau ◽  
Ronald Brown ◽  
Andrew M. Luks ◽  
Manohar L. Sharma ◽  
...  
Keyword(s):  
Steady State ◽  
Infusion Rate ◽  
Cholinesterase Activity ◽  
Hill Equation ◽  
Trans Isomers ◽  
Train Of Four ◽  
Steady State Plasma Concentration ◽  
The Hill ◽  
Effect Of Age ◽  
Cis Isomer

Background The authors previously showed that children require larger infusion rates of mivacurium than adults to maintain target twitch depression. Here, they determined whether there are differences between children and adults in mivacurium's pharmacokinetic and pharmacodynamic properties. Methods Twenty-seven patients aged 1-58 yr were anesthetized with nitrous oxide and isoflurane. Cholinesterase activity and adductor pollicis twitch tension in response to train-of-four stimuli were measured. Mivacurium was infused, targeting 90% twitch depression. When twitch was stably depressed 85%-95% for 10 min with no change in infusion rate for 15 min, plasma was sampled to determine concentrations of mivacurium's stereoisomers. Clearance of the trans-trans (Cl(trans-trans)) and cis-trans (Cl(cis-trans)) isomers was determined as the mivacurium infusion rate (adjusted for isomer composition) divided by the concentration of that isomer. Using the Hill equation, assuming equipotency of the trans-trans and cis-trans isomers, and ignoring the contribution of the nonpotent cis-cis isomer, the authors estimated the steady state plasma concentration yielding 90% twitch depression, C90. The effect of age on cholinesterase activity, the infusion rate depressing twitch tension by 90% (IR90), C90, Cl(trans-trans), and Cl(cis-trans) was determined using linear regression. Results Cholinesterase activity, IR90, and C90 did not vary with age. Both Cl(trans-trans) (r2 = 0.19, P = 0.01) and Cl(cis-trans) (r2 = 0.19, P = 0.02) decreased with age. Conclusion Clearance of mivacurium's potent isomers is larger in younger patients, consistent with the larger mivacurium infusion requirement in children than in adults reported previously.

Linking ‘Halal’ Friendly Hotel Attributes and Customer Satisfaction:The Islamic Tourism Sector

2016 ◽  
Vol 4 (4) ◽  
pp. 43
Author(s):  
Lennora Putit ◽  
Mazzini Muda ◽  
Ainul Nadzirah Mahmood ◽  
Nor Zafirah Ahmad Taufek ◽  
Norhayati Wahib
Keyword(s):  
Customer Satisfaction ◽  
Dress Code ◽  
Significant Relationships ◽  
Tourism Sector ◽  
Managerial Implications ◽  
Halal Food ◽  
Increasing Demand ◽  
Islamic Dress ◽  
The Relationship ◽  
Survey Questionnaires

An increasing demand for Islamic tourism has driven the concept of a ‘Halal’ (or permissible) friendly hotel into another level of business insight within the consumers’ travel market. The concept via its unique value proposition has rapidly become very attractive not only to Muslim tourists, but also to non-Muslim tourists globally. This study aims to examine the relationship linking ‘Halal’ friendly hotel attributes and customer satisfaction. Using purposive sampling, a total of 410 survey questionnaires were distributed to targeted respondents with only 323 usable feedbacks and used for data analysis. Regression results revealed that four main “Halal-friendly hotel” attributes have significant relationships with customer satisfaction. These include prayer facilities, Halal food, Islamic dress code and general Islamic morality. Of these four attributes, prayer facilities proved to have the most significant impact on customer satisfaction. Findings and managerial implications were further discussed in this article.

Mast Cells as a Double-Edged Sword in Immunity: Their Function in Health and Disease. First of Two Parts

2020 ◽  
Vol 20 (5) ◽  
pp. 654-669
Author(s):  
Thea Magrone ◽  
Manrico Magrone ◽  
Emilio Jirillo
Keyword(s):  
Steady State ◽  
Mast Cells ◽  
Immune Cells ◽  
Food Antigens ◽  
Health And Disease ◽  
The Relationship

Mast cells (MCs) have recently been re-interpreted in the context of the immune scenario in the sense that their pro-allergic role is no longer exclusive. In fact, MCs even in steady state conditions maintain homeostatic functions, producing mediators and intensively cross-talking with other immune cells. Here, emphasis will be placed on the array of receptors expressed by MCs and the variety of cytokines they produce. Then, the bulk of data discussed will provide readers with a wealth of information on the dual ability of MCs not only to defend but also to offend the host. This double attitude of MCs relies on many variables, such as their subsets, tissues of residency and type of stimuli ranging from microbes to allergens and food antigens. Finally, the relationship between MCs with basophils and eosinophils will be discussed.

Whos Chatting?: Interplay between Personality and WhatsApp Use

2015 ◽  
Vol 4 (4) ◽  
Author(s):  
Himanshu Rajput
Keyword(s):  
Logistic Regression ◽  
Multiple Regression ◽  
Big Five ◽  
Personality Assessment ◽  
The Internet ◽  
Big Five Inventory ◽  
Significant Relationships ◽  
Indian Context ◽  
High Penetration ◽  
The Relationship

Smartphone-based messaging applications have shown phenomenal growth with the proliferation of the internet coupled with the high penetration of smartphones into masses. The current study is an attempt to understand the relationship between the individuals personality and their use of WhatsApp, a popular smartphone-based messaging application in Indian context. For personality assessment the study takes Big Five Inventory. A questionnaire consisting items on individual WhatsApp use and Big Five Inventory was administered to students in an Indian University. Multiple regression and logistic regression revealed significant relationships between personality and WhatsApp usage and use of its different inbuilt functions.

scholarly journals How Is Sleep Related to Anxiety or Depression in Older Adults With Dementia?

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 619-619
Author(s):  
Yeji Hwang ◽  
Nancy Hodgson
Keyword(s):  
Anxiety And Depression ◽  
Regression Analyses ◽  
Subjective Sleep Quality ◽  
Subjective Sleep ◽  
Significant Relationships ◽  
People With Dementia ◽  
The Family ◽  
Study Participants ◽  
Anxiety Depression ◽  
The Relationship

Abstract Anxiety and depression are one of the most distressing symptoms for the family caregivers. Little is known about the relationship between sleep impairments and anxiety/depression in this population and how objective and subjective sleep measures differ in relation to anxiety. This study was designed to examine the relationship between sleep impairments and anxiety/depression in people with dementia, using both subjective and objective sleep measures. Among the 170 study participants, 50% (n=85) reported to have anxiety/depression. In univariate logistic regression analyses on anxiety/depression, adjusting for dementia stage, people with more subjective sleep impairment had higher odds of having anxiety/depression (OR=1.111; 95% CI: 1.020-1.211, p=0.016) and people with poorer subjective sleep quality had higher odds of having anxiety/depression (OR=1.702; 95% CI: 1.046-2.769, p=0.032). Objective sleep measures from actigraphy did not show any significant relationships to anxiety/depression. The results suggest that subjective sleep measures are closely related to anxiety/depression in this population.

scholarly journals Estimation of resistance force at steady-state sinkage for cylindrical wheel-typed lunar/planetary exploration rovers with function of push–pull locomotion

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Daisuke Fujiwara ◽  
Naoki Tsujikawa ◽  
Tetsuya Oshima ◽  
Kojiro Iizuka
Keyword(s):  
Steady State ◽  
Estimation Method ◽  
Planetary Exploration ◽  
Experimental Result ◽  
Resistance Force ◽  
Estimation Model ◽  
Loose Soil ◽  
Key Factor ◽  
The Relationship ◽  
Resistance Forces

Abstract Planetary exploration rovers have required a high traveling performance to overcome obstacles such as loose soil and rocks. Push-pull locomotion rovers is a unique scheme, like an inchworm, and it has high traveling performance on loose soil. Push-pull locomotion uses the resistance force by keeping a locked-wheel related to the ground, whereas the conventional rotational traveling uses the shear force from loose soil. The locked-wheel is a key factor for traveling in the push-pull scheme. Understanding the sinking behavior and its resistance force is useful information for estimating the rover’s performance. Previous studies have reported the soil motion under the locked-wheel, the traction, and the traveling behavior of the rover. These studies were, however, limited to the investigation of the resistance force and amount of sinkage for the particular condition depending on the rover. Additionally, the locked-wheel sinks into the soil until it obtains the required force for supporting the other wheels’ motion. How the amount of sinkage and resistance forces are generated at different wheel sizes and mass of an individual wheel has remained unclear, and its estimation method hasn’t existed. This study, therefore, addresses the relationship between the sinkage and its resistance force, and we analyze and consider this relationship via the towing experiment and theoretical consideration. The results revealed that the sinkage reached a steady-state value and depended on the contact area and mass of each wheel, and the maximum resistance force also depends on this sinkage. Additionally, the estimation model did not capture the same trend as the experimental results when the wheel width changed, whereas, the model captured a relatively the same trend as the experimental result when the wheel mass and diameter changed.

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