Reproducibility of Three Methods of Renal Clearance Estimation without Blood Samples by Means of 99mTc-DTPA

Author(s):  
A. Piepsz ◽  
J. L. Froideville ◽  
J. Kinthaert ◽  
H. R. Ham
2015 ◽  
Vol 101 (1) ◽  
pp. e1.15-e1
Author(s):  
Pieter De Cock ◽  
Joseph Standing ◽  
Charlotte Barker ◽  
Annick de Jaeger ◽  
Mieke Carlier ◽  
...  

BackgroundAmoxicillin/clavulanate is commonly used to treat community-acquired infections on the pediatric intensive care unit. Few data are available to guide dosing in this vulnerable population.MethodsThis prospective pharmacokinetic study enrolled patients admitted to the pediatric intensive care unit in whom intravenous amoxicillin-clavulanate was indicated (25–35 mg/kg q6h). Serial blood samples were obtained following the first and steady-state doses and amoxicillin/clavulanate concentrations were measured by a validated high-pressure liquid chromatography (HPLC)-tandem mass spectrometry method. Population pharmacokinetic analysis and Monte Carlo simulations were conducted using NONMEM’ 7.3.ResultsThree hundred twenty-five amoxicillin and 151 clavulanate blood samples were collected from 50 patients with a median age of 2.58 years (range: 0.08–15 years). A 3-compartment model for amoxicillin and a two-compartment model for clavulanate best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, serum Cystatin C (sCysC) ‘as a marker for renal function’ and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanate were 17.97 L/H/70 kg (95% CI:15.33–21.30 L/H/70 kg) and 12.20 L/H/70 kg (95% CI:10.54–14.55 L/H/70 kg), respectively. Four hourly dosing of 25 mg/kg (based on the amoxicillin component) was required to achieve 40% of the dosing interval for amoxicillin concentrations to be above MIC, and for clavulanate levels to be maintained above 2 mg/L. For patients with augmented renal function a 1 hour infusion was preferable to bolus dosing to achieve the therapeutic target.ConclusionsCurrent dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks treatment failure in critically ill children.


2018 ◽  
Vol 88 (3-4) ◽  
pp. 151-157 ◽  
Author(s):  
Scott W. Leonard ◽  
Gerd Bobe ◽  
Maret G. Traber

Abstract. To determine optimal conditions for blood collection during clinical trials, where sample handling logistics might preclude prompt separation of erythrocytes from plasma, healthy subjects (n=8, 6 M/2F) were recruited and non-fasting blood samples were collected into tubes containing different anticoagulants (ethylenediaminetetra-acetic acid (EDTA), Li-heparin or Na-heparin). We hypothesized that heparin, but not EDTA, would effectively protect plasma tocopherols, ascorbic acid, and vitamin E catabolites (α- and γ-CEHC) from oxidative damage. To test this hypothesis, one set of tubes was processed immediately and plasma samples were stored at −80°C, while the other set was stored at 4°C and processed the following morning (~30 hours) and analyzed, or the samples were analyzed after 6 months of storage. Plasma ascorbic acid, as measured using HPLC with electrochemical detection (LC-ECD) decreased by 75% with overnight storage using EDTA as an anticoagulant, but was unchanged when heparin was used. Neither time prior to processing, nor anticoagulant, had any significant effects upon plasma α- or γ-tocopherols or α- or γ-CEHC concentrations. α- and γ-tocopherol concentrations remained unchanged after 6 months of storage at −80°C, when measured using either LC-ECD or LC/mass spectrometry. Thus, refrigeration of whole blood at 4°C overnight does not change plasma α- or γ-tocopherol concentrations or their catabolites. Ascorbic acid is unstable in whole blood when EDTA is used as an anticoagulant, but when whole blood is collected with heparin, it can be stored overnight and subsequently processed.


2010 ◽  
Vol 41 (02) ◽  
Author(s):  
N Shazi ◽  
A Böss ◽  
HJ Merkel ◽  
F Scharbert ◽  
D Hannak ◽  
...  

1977 ◽  
Vol 16 (03) ◽  
pp. 100-103 ◽  
Author(s):  
C. Schümichen ◽  
J. Waiden ◽  
G. Hoffmann

SummaryThe kinetic data of two different 99mTc-Sn-pyrophosphate compounds (compound A and B) were evaluated in non-adult rats. Only compound A concentrated in bone. Both compounds dispersed rapidly in the intravascular as well as the extravascular space. The plasma protein bond of both compounds increased with time after injection and impaired both the renal clearance of both compounds and the bone clearance of compound A. The renal clearance of both compounds was somewhat above that of 5 1Cr-EDTA. It is concluded that compound A and B is mainly excreted by glomerular filtration. About one fourth of the glomerular filtrate of compound B is reabsorbed and accumulated by the tubular cells.


1994 ◽  
Vol 71 (06) ◽  
pp. 727-730 ◽  
Author(s):  
M J Kovacs ◽  
A Wong ◽  
K MacKinnon ◽  
K Weir ◽  
M Keeney ◽  
...  

SummaryThe INR system was developed to standardize PT reporting in patients on oral anticoagulants. We prospectively collected blood samples from 29 patients with liver impairment (INR 1.5-3.5). Control patients were on warfarin (n = 31). PT’s were measured on an ACL-300 with three thromboplastin reagents. INR’s were calculated using instrument specific ISI’s. Other tests performed were FDP’s, fibrinogen, aPTT, factors II, V, VII and X. The INR’s for each patient in the study population using the three thromboplastin reagents were significantly different (p = 0.0001). Those for the control population were not (p = 0.0658). Fibrinogen, factors V, II and X were different at the 5% level of significance between the populations. FDP’s were detected in 17 study subjects. The INR system is not valid for comparison of patients with liver impairment because different reagents do not give the same INR for the same sample. It is, however, no less valid than the use of PT with different thromboplastin reagents. Further study is recommended.


1990 ◽  
Vol 64 (01) ◽  
pp. 117-120 ◽  
Author(s):  
Alessandra Casonato ◽  
M Teresa Sartori ◽  
Luigi de Marco ◽  
Antonio Girolami

SummaryWe have investigated the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion on platelet count and bleeding time in 4 patients with type IIB von Willebrand’s disease (vWd). Three of four patients showed a normalization of the bleeding time within 1 h after the infusion, while bleeding time was not modified in the fourth. In accordance with the literature, thrombocytopenia was observed after DDAVP infusion, but this thrombocytopenia was due to the anticoagulants used for blood collection. In two patients (F. I., G. F.) no thrombocytopenia was observed when platelets were counted by fingerstick method but there was a 20% platelet decrease in blood samples collected in sodium citrate and a 50% decrease in samples collected in EDTA. Dramatic falls in platelet counts (70–95%) were observed in the additional two patients (C. A., D.Z.) after DDAVP infusion, when both sodium citrate or EDTA were used as anticoagulants. In the latter two patients there was also a 50% decrease in platelet count when the fingerstick method was used. The decrease in the patient’s platelet count in EDTA samples after DDAVP infusion could be prevented, in part, by the previous additions of an anti GPIb monoclonal antibody and an anti GPIIb-IIIa monoclonal antibody.Thus, the thrombocytopenia observed in the four IIB vWd patients studied after DDAVP infusion seems to be, at least partially, a pseudothrombocytopenia depending on the calcium concentration in the blood samples and the availability of GPIb and GPIIb-IIIa receptors. These findings and the normalization of the bleeding time observed in three of the four patients has led us to reconsider the possible use of DDAVP in the treatment of our IIB vWd patients.


1989 ◽  
Vol 62 (04) ◽  
pp. 1107-1111 ◽  
Author(s):  
Hugo C Castro-Faria-Neto ◽  
Patricia T Bozza ◽  
Marco A Martins ◽  
Paulo M F L Dias ◽  
Patricia M R Silva ◽  
...  

SummaryThe injection of PAP (6 μg/kg, i. v.) induced, in rats, haemoconcentration accompanied by an increase in the platelet number, as attested by the counts of platelets in blood samples diluted in formalin-free EDTA solution. This increase was significant at 15 min, peaked from 1 to 4 h and returned to basal levels 24 h after the lipid administration. The release of platelets induced by PAP was inhibited dose-dependently by specific PAP receptor antagonists such as WEB 2086 (0.5-2 mg/kg), BN 52021 and 48740 RP (5-25 mg/kg). Furthermore, platelet mobilization was clearly impaired in splenectomized animals stimulated by PAP, whereas thrombocytopenia and haemoconcentration by the same stimulus were intact. It was also noted that a second injection of PAP, 24 h after the initial stimulation with the lipid, failed to induce an increase in platelet counts, indicating autodesensitization. Desensitization to PAP or pretreatment with PAP antagonists clearly prevented the increase in the platelet counts after stimulation by adrenaline (15 μg/kg). These findings suggest that, in rats, PAP can induce release of platelets by a spleen-dependent mechanism and that this lipid may be relevant to the thrombocytosis triggered by adrenaline.


1994 ◽  
Vol 72 (05) ◽  
pp. 672-675 ◽  
Author(s):  
Nicolas W Shammas ◽  
Michael J Cunningham ◽  
Richard M Pomearntz ◽  
Charles W Francis

SummaryTo characterize the extent of early activation of the hemostatic system following angioplasty, we obtained blood samples from the involved coronary artery of 11 stable angina patients during the procedure and measured sensitive markers of thrombin formation (fibrino-peptide A, prothrombin fragment 1.2, and soluble fibrin) and of platelet activation ((3-thromboglobulin). Levels of hemostatic markers in venous blood obtained from 14 young individuals with low pretest probability for coronary artery disease were not significantly different from levels in venous blood or intracoronary samples obtained prior to angioplasty. Also, there was no translesional (proximal and distal to the lesion) gradient in any of the hemostatic markers before or after angioplasty in samples obtained between 18 and 21 min from the onset of the first balloon inflation. Furthermore, no significant difference was noted between angioplasty and postangioplasty intracoronary concentrations. We conclude that intracoronary hemostatic activation does not occur in the majority of patients during and immediately following coronary angioplasty when high doses of heparin and aspirin are administered.


1994 ◽  
Vol 72 (01) ◽  
pp. 084-088 ◽  
Author(s):  
E M Duncan ◽  
C R Casey ◽  
B M Duncan ◽  
J V Lloyd

SummaryThe aim of this study was to determine whether the concentration of trisodium citrate used to anticoagulate blood has an effect on the INR of the sample and the ISI of the thromboplastin. Five thromboplastins including and Australian reference material were used to measure the prothrombin time of normal and patient samples collected into two concentrations of trisodium citrate - 109 mM and 129 mM. There was no effect of citrate concentration on the INRs determined with the reference material. However for the other four thromboplastins there was a significant difference between INRs for the two citrate groups. The prothrombin times of the samples collected into 129 mM were longer than those collected into 109 mM. This difference was only slight in normal plasma but more marked in patients receiving oral anticoagulants, causing the INRs for patient plasmas collected into 129 mM citrate to be higher then the corresponding samples collected into 109 mM citrate.From orthogonal regression of log prothrombin times by the reference method against each thromboplastin, we found that the ISI for each thromboplastin was approximately 10% lower when determined with samples collected into 129 mM citrate than with samples collected into 109 mM. These results suggest that the concentration of trisodium citrate used for collection of blood samples can affect the calculation of the INR and the calibration of the ISI of thromboplastin. This was found both for commercial thromboplastins prepared by tissue extraction and for a recombinant tissue factor.


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