A System for Individualized Dosing of Intravenous Aminophylline Using a Programmable Calculator

PEDIATRICS ◽  
1984 ◽  
Vol 73 (1) ◽  
pp. 64-67
Author(s):  
J. Chris Mitsuoka ◽  
Richard J. Fleck
Keyword(s):  
Steady State ◽  
Serum Sample ◽  
Drug Exposure ◽  
Plasma Concentrations ◽  
Dose Administration ◽  
Programmable Calculator ◽  
Concentration Determination ◽  
A Value ◽  
Individualized Dosing ◽  
History Of

A program that calculates a value of clearance for an individual patient prior to reaching steady state in the early stages of aminophylline therapy is presented. The program is written for the Texas Instruments TI-59 programmable calculator and may be used with or without the PC-100C printer. The program can provide clinically useful information concerning projected plasma concentrations prior to reaching steady state with an accurate history of the dose administration and serum concentration determination. If the patient has not received xanthene therapy prior to admission, only one serum sample is required. If there has been prior drug exposure, a second serum sample is required. An iterative technique, which would be impractical to use without calculator assistance, is employed to make these determinations.

scholarly journals Exposure-Response Relationships for Isavuconazole in Patients with Invasive Aspergillosis and Other Filamentous Fungi

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
Amit V. Desai ◽  
Laura L. Kovanda ◽  
William W. Hope ◽  
David Andes ◽  
Johan W. Mouton ◽  
...  
Keyword(s):  
Steady State ◽  
Invasive Aspergillosis ◽  
Filamentous Fungi ◽  
Aspartate Aminotransferase ◽  
Drug Exposure ◽  
Fungal Infections ◽  
Plasma Concentrations ◽  
Water Soluble ◽  
Therapeutic Drug ◽  
Exposure Response

ABSTRACT Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and infections by other filamentous fungi from the SECURE clinical trial. Two hundred thirty-one patients who received the clinical dosing regimen and had exposure parameters were included in the analysis. The primary drug exposure parameters included were predicted trough steady-state plasma concentrations, predicted trough concentrations after 7 and 14 days of drug administration, and area under the curve estimated at steady state (AUCss). The exposure parameters were analyzed against efficacy endpoints that included all-cause mortality through day 42 in the intent-to-treat (ITT) and modified ITT populations, data review committee (DRC)-adjudicated overall response at end of treatment (EOT), and DRC-adjudicated clinical response at EOT. The safety endpoints analyzed were elevated or abnormal alanine aminotransferase, increased aspartate aminotransferase, and a combination of the two. The endpoints were analyzed using logistic regression models. No statistically significant relationship (P > 0.05) was found between isavuconazole exposure and either efficacy or safety endpoints. The lack of association between exposure and efficacy indicates that the isavuconazole exposures achieved by clinical dosing were appropriate for treating the infecting organisms in the SECURE study and that increases in alanine or aspartate aminotransferase were not related to increase in exposures. Without a clear relationship, there is no current clinical evidence for recommending routine therapeutic drug monitoring for isavuconazole.

CYP3A4 phenotyping with midazolam to predict sunitinib exposure.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2592-2592
Author(s):  
Nielka P van Erp ◽  
Djoeke de Wit ◽  
Alex Sparreboom ◽  
Jan den Hartigh ◽  
Margret den Hollander ◽  
...  
Keyword(s):  
Steady State ◽  
Drug Exposure ◽  
Linear Regression Analysis ◽  
Plasma Concentrations ◽  
Systemic Exposure ◽  
Considerable Proportion ◽  
Cyp3a4 Activity ◽  
Standard Dosage ◽  
Patients At Risk ◽  
The Relationship

2592 Background: Patients treated with sunitinib show high inter-patient variability in drug exposure (40-60%), which is largely unexplained. Since sunitinib is metabolized by CYP3A4, variability in the activity of this enzyme may explain a considerable proportion of the observed variability. We therefore prospectively studied the relationship between CYP3A4 activity and systemic exposure to sunitinib. Methods: In fifteen patients treated with sunitinib in a four weeks “on” – two weeks “off” regimen the pharmacokinetics of sunitinib and its active metabolite SU12662 were assessed. To determine sunitinib+SU12662 steady-state exposure, samples were collected over 24hrs after at least 14 days of sunitinib therapy. To assess CYP3A4 activity, midazolam 7.5mg orally was administered on the final day of the two weeks “off”. Plasma concentrations were measured over a period of 7hrs to determine midazolam exposure. Exposures (AUC) were calculated using a trapezoidal approach (Phoenix WinNonlin v6.3). The relationship between CYP3A4 activity (midazolam exposure) and sunitinib+SU12662 exposure was determined by linear regression analysis. The percentage of variability in sunitinib+SU12662 exposure that could be explained by CYP3A4 activity was calculated by Pearson’s correlation. In addition, the correlation between sunitinib+SU12662 Ctrough levels and sunitinib+SU12662 exposure was assessed. Results: A strong correlation between midazolam exposure (AUC0-7hr) and steady-state sunitinib+SU12662 exposure (AUC0-24hr) was found (p= 0.002); CYP3A4 activity explained 55% of the observed inter-patient PK variability of sunitinib+SU12662. Furthermore sunitinib+SU12662 Ctrough levels were highly predictive (96%) for overall sunitinib+SU12662 exposure (AUC0-24hr). Conclusions: Midazolam as a phenotyping probe could be useful before start of sunitinib therapy to identify patients at risk for under- respectively overtreatment at a standard dosage regimen. Therefore, CYP3A4 phenotyping could be useful to individualize sunitinib therapy. Additionally, sunitinib+SU12662 trough levels are highly predictive for sunitinib+SU12662 exposure and thus can be used for monitoring and guiding sunitinib therapy in clinical practice. Clinical trial information: NCT01743300.

Analysis of count data in the setting of cervical cancer detection

2020 ◽  
Vol 68 (6) ◽  
pp. 1196-1198
Author(s):  
Christina G Bracamontes ◽  
Thelma Carrillo ◽  
Jane Montealegre ◽  
Leonid Fradkin ◽  
Michele Follen ◽  
...  
Keyword(s):  
Sexual Abuse ◽  
Count Data ◽  
Pap Smear ◽  
Negative Binomial ◽  
El Paso ◽  
Language Preference ◽  
A Value ◽  
History Of ◽  
Zip Model ◽  
Endocervical Canal

Women with an abnormal Pap smear are often referred to colposcopy, a procedure during which endocervical curettage (ECC) may be performed. ECC is a scraping of the endocervical canal lining. Our goal was to compare the performance of a naïve Poisson (NP) regression model with that of a zero-inflated Poisson (ZIP) model when identifying predictors of the number of distress/pain vocalizations made by women undergoing ECC. Data on women seen in the colposcopy clinic at a medical school in El Paso, Texas, were analyzed. The outcome was the number of pain vocalizations made by the patient during ECC. Six dichotomous predictors were evaluated. Initially, NP regression was used to model the data. A high proportion of patients did not make any vocalizations, and hence a ZIP model was also fit and relative rates (RRs) and 95% CIs were calculated. AIC was used to identify the best model (NP or ZIP). Of the 210 women, 154 (73.3%) had a value of 0 for the number of ECC vocalizations. NP identified three statistically significant predictors (language preference of the subject, sexual abuse history and length of the colposcopy), while ZIP identified one: history of sexual abuse (yes vs no; adjusted RR=2.70, 95% CI 1.47 to 4.97). ZIP was preferred over NP. ZIP performed better than NP regression. Clinicians and epidemiologists should consider using the ZIP model (or the zero-inflated negative binomial model) for zero-inflated count data.

scholarly journals The influence of associative reward learning on motor inhibition

2021 ◽  
Author(s):  
Janina Rebecca Marchner ◽  
Claudia Preuschhof
Keyword(s):  
Experimental Design ◽  
Action Control ◽  
Reward Learning ◽  
Behavioural Activation ◽  
Motor Inhibition ◽  
A Value ◽  
Directed Action ◽  
History Of ◽  
Pavlovian Learning ◽  
Subsequent Task

AbstractStimuli that predict a rewarding outcome can cause difficulties to inhibit unfavourable behaviour. Research suggests that this is also the case for stimuli with a history of reward extending these effects on action control to situations, where reward is no longer accessible. We expand this line of research by investigating if previously reward-predictive stimuli promote behavioural activation and impair motor inhibition in a second unrelated task. In two experiments participants were trained to associate colours with a monetary reward or neutral feedback. Afterwards participants performed a cued go/no-go task, where cues appeared in the colours previously associated with feedback during training. In both experiments training resulted in faster responses in rewarded trials providing evidence of a value-driven response bias as long as reward was accessible. However, stimuli with a history of reward did not interfere with goal-directed action and inhibition in a subsequent task after removal of the reward incentives. While the first experiment was not conclusive regarding an impact of reward-associated cues on response inhibition, the second experiment, validated by Bayesian statistics, clearly questioned an effect of reward history on inhibitory control. This stands in contrast to earlier findings suggesting that the effect of reward history on subsequent action control is not as consistent as previously assumed. Our results show that participants are able to overcome influences from Pavlovian learning in a simple inhibition task. We discuss our findings with respect to features of the experimental design which may help or complicate overcoming behavioural biases induced by reward history.

scholarly journals The formation of vortices from a surface of discontinuity

1931 ◽  
Vol 134 (823) ◽  
pp. 170-192 ◽  
Keyword(s):  
Steady State ◽  
Plane Surface ◽  
Equations Of Motion ◽  
Steady Motion ◽  
Small Oscillations ◽  
Approximate Form ◽  
History Of ◽  
State Increase ◽  
Liquid Surfaces

Helmholtz was the first to remark on the instability of those “liquid surfaces” which separate portions of fluid moving with different velocities, and Kelvin, in investigating the influence of wind on waves in water, supposed frictionless, has discussed the conditions under which a plane surface of water becomes unstable. Adopting Kelvin’s method, Rayleigh investigated the instability of a surface of discontinuity. A clear and easily accessible rendering of the discussion is given by Lamb. The above investigations are conducted upon the well-known principle of “small oscillations”—there is a basic steady motion, upon which is superposed a flow, the squares of whose components of velocity can be neglected. This method has the advantage of making the equations of motion linear. If by this method the flow is found to be stable, the equations of motion give the subsequent history of the system, for the small oscillations about the steady state always remain “small.” If, however, the method indicates that the system is unstable, that is, if the deviations from the steady state increase exponentially with the time, the assumption of small motions cannot, after an appropriate interval of time, be applied to the case under consideration, and the equations of motion, in their approximate form, no longer give a picture of the flow. For this reason, which is well known, the investigations of Rayleigh only prove the existence of instability during the initial stages of the motion. It is the object of this note to investigate the form assumed by the surface of discontinuity when the displacements and velocities are no longer small.

Equation Error

PEDIATRICS ◽  
1984 ◽  
Vol 74 (1) ◽  
pp. 169-169
Author(s):  
KENNETH MCCORMICK
Keyword(s):  
Loading Dose ◽  
Programmable Calculator ◽  
Duration Of Therapy ◽  
State Duration ◽  
Individualized Dosing ◽  
Equation Error

To the Editor.— I believe there is an error in the article entitled "A System for Individualized Dosing of Intravenous Aminophylline Using a Programmable Calculator" by J. Chris Mitsuoka and Richard J. Fleck (Pediatrics 1984;73:64-67). In the first equation, the first term Cpo e-Ke(t-t') should be Cpo e-Ke(t + t') if t represents the time elapsed after the infusion has commenced. The paper is confusing as to exactly what t represents; the authors state "duration of therapy" but does therapy begin with the loading dose or with the infusion.

scholarly journals Prediction of steady-state verapamil plasma concentrations in children and adults

1982 ◽  
Vol 32 (2) ◽  
pp. 172-181 ◽  
Author(s):  
John G Wagner ◽  
Albert P Rocchini ◽  
John Vasiliades
Keyword(s):  
Steady State ◽  
Plasma Concentrations

Effects of temperature on acid-base balance and ventilation in desert iguanas

1981 ◽  
Vol 51 (2) ◽  
pp. 452-460 ◽  
Author(s):  
P. E. Bickler
Keyword(s):  
Steady State ◽  
Pulmonary Ventilation ◽  
Respiratory Acidosis ◽  
Lung Ventilation ◽  
Acid Base Balance ◽  
Acid Base ◽  
Arterial Ph ◽  
Blood Relative ◽  
Base Balance ◽  
History Of

The effects of constant and changing temperatures on blood acid-base status and pulmonary ventilation were studied in the eurythermal lizard Dipsosaurus dorsalis. Constant temperatures between 18 and 42 degrees C maintained for 24 h or more produced arterial pH changes of -0.0145 U X degrees C-1. Arterial CO2 tension (PCO2) increased from 9.9 to 32 Torr plasma [HCO-3] and total CO2 contents remained constant at near 19 and 22 mM, respectively. Under constant temperature conditions, ventilation-gas exchange ratios (VE/MCO2 and VE/MO2) were inversely related to temperature and can adequately explain the changes in arterial PCO2 and pH. During warming and cooling between 25 and 42 degrees C arterial pH, PCO2 [HCO-3], and respiratory exchange ratios (MCO2/MO2) were similar to steady-state values. Warming and cooling each took about 2 h. During the temperature changes, rapid changes in lung ventilation following steady-state patterns were seen. Blood relative alkalinity changed slightly with steady-state or changing body temperatures, whereas calculated charge on protein histidine imidazole was closely conserved. Cooling to 17-18 degrees C resulted in a transient respiratory acidosis correlated with a decline in the ratio VE/MCO2. After 12-24 h at 17-18 degrees C, pH, PCO2, and VE returned to steady-state values. The importance of thermal history of patterns of acid-base regulation in reptiles is discussed.

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