Radiation safety considerations for the bone seeking radiopharmaceuticals

2009 ◽  
Vol 48 (01) ◽  
pp. 37-43 ◽  
Author(s):  
A. Hoekstra ◽  
J. M. H. de Klerk ◽  
P. P. van Rijk ◽  
B. A. Zonnenberg ◽  
M. G. E. H. Lam
Keyword(s):  
Gamma Radiation ◽  
Radiation Safety ◽  
Area Under The Curve ◽  
Beta Radiation ◽  
Time Data ◽  
Rate Versus ◽  
Respective Contribution ◽  
Effective Doses ◽  
Safety Considerations ◽  
Measured Exposure

SummaryThe radiation exposure to bystanders from 89SrCl2, 186Re-HEDP and 153Sm-EDTMP, is generally thought to be caused by “bremsstrahlung” and gamma-radiation, with negligible contribution from beta-radiation. The latter assumption may be erroneous. The aim of this prospective study was the investigation of radiation safety after treatment with these radiopharmaceuticals. The radiation field around treated patients was characterized and the magnitude estimated. Patients, methods: 33 patients (30 prostate carcinoma, 3 breast carcinoma) were treated with 150 MBq 89SrCl2 (9 patients), 1295 MBq 186Re-HEDP (12 patients) or 37 MBq/kg 153Sm-EDTMP (12 patients). External exposure rates at 30 cm from the patient were measured at times 0 to 72 h post-injection. To evaluate the respective contribution of Bremsstrahlung, beta- and gamma-radiation, a calibrated survey meter was used, equipped with a shutter. For each patient, the measured exposure rate-versus-time data were fit to a curve and the curve integrated (area under the curve) to estimate the total exposure. Results: For 29/33 patients the total ambient equivalent doses (mean ± 1 standard deviation [SD]) based on the integral of the fitted curve were 2.1 ± 1.2 mSv for 89SrCl2, 3.3 ± 0.6 mSv for 186Re-HEDP and 2.8 ± 0.6 mSv for 153Sm-EDTMP. Beta-radiation contributes significantly to these doses ( >99% for 89SrCl2, 87% for 186Re-HEDP and 27% for 153Sm-EDTMP). The effective doses (at 30 cm) are < 0.1 mSv for 89SrCl2, 0.3 mSv for 186Re-HEDP and 1.6 mSv for 153Sm-EDTMP. Conclusion: Patients treated with 89SrCl2, 186Re-HEDP or 153Sm-EDTMP emit a spectrum of radiation, including non-negligible beta-radiation. With specific instructions effective doses to bystanders are acceptable.

scholarly journals То the problem of irradiation dosing of population in radionuclde studies

2001 ◽  
Vol 82 (5) ◽  
pp. 383-385
Author(s):  
V. G. Morozov ◽  
R. K. Ismagilov ◽  
V. F. Chuprun
Keyword(s):  
Gamma Radiation ◽  
Radiation Safety ◽  
Radiation Doses ◽  
Safety Standards ◽  
The Given

It is shown that with the introduction of new wording of the radiation safety standards - 99 regulating powers of gamma-radiation doses at the distance of one meter from the patient, treated by radiopharma-ceutical drugs, should not exceed three mcSv/h. The number noted is obviously set too high and should be substantiated. Abolition of the adopted standards and statement of the given regulations in the radiation safety standards 99 in new wording is not proven enough substantiated.

scholarly journals Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
E. T. Van Matre ◽  
I. Teitelbaum ◽  
T. H. Kiser
Keyword(s):  
Peritoneal Dialysis ◽  
Half Life ◽  
Peritoneal Fluid ◽  
Area Under The Curve ◽  
Terminal Phase ◽  
Dialysis Patients ◽  
Time Data ◽  
Open Label ◽  
Gram Positive ◽  
Clinical Pharmacokinetics

ABSTRACT Dalbavancin offers a possible treatment option for infectious peritonitis associated with peritoneal dialysis (PD) due to its coverage of Gram-positive bacteria and pharmacokinetic properties. We aimed to evaluate the clinical pharmacokinetics (PK) and pharmacodynamics of dalbavancin in a prospective, randomized, open-label, crossover PK study of adult patients with end-stage renal disease ESRD who were receiving PD. Sampling occurred prior to a single 30-min infusion of dalbavancin at 1,500 mg and at 1, 2, 3, 4, and 6 h and 7 and 14 days postadministration. Concentration-time data were analyzed via noncompartmental analysis. Pharmacodynamic parameters against common infectious peritonitis-causing pathogens were evaluated. Ten patients were enrolled. Patients were a median of 55 years old and had a median weight of 78.2 kg, 50% were female, and 70% were Caucasian. The terminal plasma half-life of dalbavancin was 181.4 ± 35.5 h. The day 0 to day 14 dalbavancin mean area under the curve (AUC) was 40,573.2 ± 9,800.3 mg·h/liter. The terminal-phase half-life of dalbavancin within the peritoneal fluid was 4.309 × 108 ± 1.140 × 109 h. The day 0 to day 14 dalbavancin mean peritoneal fluid AUC was 2,125.0 ± 1,794.3 mg·h/liter. The target plasma AUC/MIC was attained with the intravenous dose in all 10 patients for all Staphylococcus and Streptococcus species at the recommended MIC breakpoints. The intraperitoneal arm of the study was stopped early, because the first 3 patients experienced moderate to severe pain and bloating within 1 h following the administration of dalbavancin. Dalbavancin at 1,500 mg administered intravenously can be utilized without dose adjustment in peritoneal dialysis patients and will likely achieve the necessary peritoneal fluid concentrations to treat peritonitis caused by typical Gram-positive pathogens.

scholarly journals Development of a Compact, IoT-Enabled Electronic Nose for Breath Analysis

Electronics ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 84 ◽  
Author(s):  
Akira Tiele ◽  
Alfian Wicaksono ◽  
Sai Kiran Ayyala ◽  
James A. Covington
Keyword(s):  
Electronic Nose ◽  
Area Under The Curve ◽  
Breath Analysis ◽  
Mobile App ◽  
P Value ◽  
Exhaled Breath ◽  
Time Data ◽  
Sample Tube ◽  
Heated Sample ◽  
End Tidal

In this paper, we report on an in-house developed electronic nose (E-nose) for use with breath analysis. The unit consists of an array of 10 micro-electro-mechanical systems (MEMS) metal oxide (MOX) gas sensors produced by seven manufacturers. Breath sampling of end-tidal breath is achieved using a heated sample tube, capable of monitoring sampling-related parameters, such as carbon dioxide (CO2), humidity, and temperature. A simple mobile app was developed to receive real-time data from the device, using Wi-Fi communication. The system has been tested using chemical standards and exhaled breath samples from healthy volunteers, before and after taking a peppermint capsule. Results from chemical testing indicate that we can separate chemical standards (acetone, isopropanol and 1-propanol) and different concentrations of isobutylene. The analysis of exhaled breath samples demonstrate that we can distinguish between pre- and post-consumption of peppermint capsules; area under the curve (AUC): 0.81, sensitivity: 0.83 (0.59–0.96), specificity: 0.72 (0.47–0.90), p-value: <0.001. The functionality of the developed device has been demonstrated with the testing of chemical standards and a simplified breath study using peppermint capsules. It is our intention to deploy this system in a UK hospital in an upcoming breath research study.

scholarly journals Emergence of power laws in the pharmacokinetics of paclitaxel due to competing saturable processes.

2008 ◽  
Vol 11 (3) ◽  
pp. 77 ◽  
Author(s):  
Jack A Tuszynski ◽  
Rebeccah E. Marsh ◽  
Michael B. Sawyer ◽  
Kenneth J.E. Vos
Keyword(s):  
Power Law ◽  
Fractional Power ◽  
Area Under The Curve ◽  
Power Laws ◽  
Dose Dependence ◽  
Power Exponent ◽  
Least Squares Regression ◽  
Time Data ◽  
Concentration Time ◽  
Wide Range

Purpose: This study presents the results of power law analysis applied to the pharmacokinetics of paclitaxel. Emphasis is placed on the role that the power exponent can play in the investigation and quantification of nonlinear pharmacokinetics and the elucidation of the underlying physiological processes. Methods: Forty-one sets of concentration-time data were inferred from 20 published clinical trial studies, and 8 sets of area under the curve (AUC) and maximum concentration (Cmax) values as a function of dose were collected. Both types of data were tested for a power law relationship using least squares regression analysis. Results: Thirty-nine of the concentration-time curves were found to exhibit power law tails, and two dominant fractal exponents emerged. Short infusion times led to tails with a single power exponent of -1.57 ± 0.14, while long infusion times resulted in steeper tails characterized by roughly twice the exponent. The curves following intermediate infusion times were characterized by two consecutive power laws; an initial short slope with the larger alpha value was followed by a crossover to a long-time tail characterized by the smaller exponent. The AUC and Cmax parameters exhibited a power law dependence on the dose, with fractional power exponents that agreed with each other and with the exponent characterizing the shallow decline. Computer simulations revealed that a two- or three-compartment model with both saturable distribution and saturable elimination can produce the observed behaviour. Furthermore, there is preliminary evidence that the nonlinear dose-dependence is correlated with the power law tails. Conclusion: Assessment of data from published clinical trials suggests that power laws accurately describe the concentration-time curves and non-linear dose-dependence of paclitaxel, and the power exponents provide insight into the underlying drug mechanisms. The interplay between two saturable processes can produce a wide range of behaviour, including concentration-time curves with exponential, power law, and dual power law tails.

scholarly journals Pharmacokinetic-Pharmacodynamic Comparison of Amphotericin B (AMB) and Two Lipid-Associated AMB Preparations, Liposomal AMB and AMB Lipid Complex, in Murine Candidiasis Models

2006 ◽  
Vol 50 (2) ◽  
pp. 674-684 ◽  
Author(s):  
D. Andes ◽  
N. Safdar ◽  
K. Marchillo ◽  
R. Conklin
Keyword(s):  
Amphotericin B ◽  
Area Under The Curve ◽  
Dosing Regimen ◽  
Multiple Dosing ◽  
Lipid Complex ◽  
Disseminated Candidiasis ◽  
Effective Doses ◽  
The Difference ◽  
Time Kill ◽  
Lipid Formulations

ABSTRACT It is generally accepted that the lipid formulations of amphotericin B (AMB) are not as potent as conventional AMB on a milligram-per-kilogram basis. We used a neutropenic murine disseminated candidiasis model to compare the in vivo potencies of AMB, liposomal AMB (L-AMB), and AMB lipid complex (ABLC) pharmacodynamically. The pharmacokinetics of the antifungals were examined in serum and in three organs commonly seeded in disseminated candidiasis (kidneys, liver, and lung). Both single-dose time-kill studies and multiple-dosing-regimen studies were used with each of the compounds. Determinations of the numbers of CFU in the kidneys were performed following the administration of three escalating single doses of the polyenes at various times over 48 h. The areas under the time-kill curves (AUTKs) for each dose level of the drugs were compared by analysis of variance (ANOVA). In the multiple-dosing-regimen studies with five Candida isolates, AMB, L-AMB, and ABLC were administered daily for 72 h. The organism burdens in the mouse kidneys were similarly used as the treatment end point. Additional multiple regimen-dosing-studies were performed with a single Candida albicans isolate, and the microbiologic outcomes in four internal organs (kidneys, liver, spleen, and lung) were examined at the end of therapy (48 h). The relationship between the dose and the drug exposure expressed by the pharmacokinetics of the dosing regimens in serum and organ tissue were analyzed by using a maximum-effect model. ANOVA was used to compare the drug exposures necessary to achieve the 25% effective dose (ED25), ED50, ED75, and 1 log10 killing. Comparison of AUTKs suggested that AMB was 4.3- to 5.9-fold more potent than either ABLC or L-AMB. The time-kill curves for both lipid formulations were very similar. In the multiple-dosing-regimen studies, AMB was 5.0- to 8.0-fold more potent than each of the lipid formulations against five Candida isolates in the kidneys. Similar differences in potency (5.1- to 7.2-fold) were observed in the other end organs. The difference in pharmacokinetics in serum accounted for much of the difference in potency between AMB and ABLC (ratio of serum ABLC area under the curve of effective doses to serum AMB area under the curve of effective doses, 1.2). The differences in the kinetics in the various end organs between AMB and L-AMB were better at explaining the disparate potencies at these infection sites (ratio of organ L-AMB area under the curve of effective doses to organ AMB area under the curve of effective doses, 1.1).

Pharmacokinetic study of clofarabine: Oral bioavailability and the effect of cimetidine on renal clearance.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13074-e13074
Author(s):  
Matthew Charles Foster ◽  
Parag Kumar ◽  
Christine Marie Walko ◽  
Anastasia Ivanova ◽  
Reginald Ewesuedo ◽  
...  
Keyword(s):  
Renal Clearance ◽  
Basolateral Membrane ◽  
Area Under The Curve ◽  
Organic Cation Transporter ◽  
Tubular Secretion ◽  
Time Data ◽  
Geometric Means ◽  
Human Trial ◽  
Organic Cation Transporter 2 ◽  
Renal Tubular

e13074 Background: Clofarabine (CLO) is a purine analog with activity in myeloid neoplasms. Its oral dosing has been based on an estimated bioavailability (F) of 49% from uncontrolled trials. Animal models suggest that CLO renal clearance (CL) may be impaired in the presence of inhibitors of organic cation transporter-2 (OCT2), which mediates transport across the renal tubular basolateral membrane. We conducted a pharmacokinetic (PK) study of CLO to determine F, and examine the effect of the OCT2 inhibitor, cimetidine (CIM) on intravenous (IV) CLO. Methods: Patients had: 1) untreated AML ≥ 60 years of age unsuited for standard induction, 2) relapsed or refractory AML, or 3) MDS after failure of ≥ 1 prior regimen. Treatment was: CLO 15 mg/m2 IV day 1, CLO 30 mg/m2 orally (PO) day 3, CLO 15 mg/m2 IV day 5 preceded by two doses of oral CIM, and CLO 30 mg/m2 PO on days 6 and 7. PK studies were obtained after CLO dosing on days 1, 3 and 5. For each dose, CLO plasma concentration was determined, and concentration-time data was analyzed by non-compartmental methods. F was determined for each patient. The geometric means of area under the curve (AUC), 0-∞, and CL for IV CLO administered after CIM doses were compared with AUC and CL for IV CLO administered without CIM. Results: Interim data for the first ten treated patients, with comparisons of PK parameters are shown in the table below. Conclusions: Using patients as their own controls, F of CLO is higher than previously estimated. AUC of CLO is increased and CL is decreased in the presence of CIM, likely owing to inhibition of OCT2-mediated renal tubular secretion. This study is the first human trial to suggest that CLO CL may be impaired in the presence of OCT2 inhibitors, such as cimetidine, trimethoprim, verapamil and nicotine. [Table: see text]

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