Vancomycin Serum Protein Binding Determination by Ultrafiltration

1988 ◽  
Vol 22 (4) ◽  
pp. 300-303 ◽  
Author(s):  
Bruce H. Ackerman ◽  
E. Howard Taylor ◽  
Keith M. Olsen ◽  
Wedad Abdel-Malak ◽  
Alexandras A. Pappas

Sixty-two serum concentrations were obtained from 12 infected patients enrolled in a vancomycin pharmacokinetic study. Both unbound and total serum vancomycin concentrations were measured using ultrafiltration and a commercial fluorescent polarization immunoassay. Ultrafiltrates were obtained by centrifugation at 1000 × g for ten minutes at room temperature and their assay indicated a range in protein binding from 7.9 to 71 percent. The mean protein binding (mean ±SD) was 41.95 ± 14.15 percent. No measurable adsorption of vancomycin onto the ultrafiltration membrane was noted. Orthogonal regression of unbound versus total vancomycin concentrations was described by the equation y=0.597x-0.362 with a correlation coefficient of 0.948.

2019 ◽  
Vol 104 (12) ◽  
pp. 5831-5839 ◽  
Author(s):  
Adrian R Martineau ◽  
Kenneth E Thummel ◽  
Zhican Wang ◽  
David A Jolliffe ◽  
Barbara J Boucher ◽  
...  

Abstract Context Vitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism. Objective To compare the influence of administering vitamin D2 vs vitamin D3 on metabolism of vitamin D3. Methods We measured baseline and 4-month serum concentrations of vitamin D3, 25-hydroxyvitamin D3 [25(OH)D3], 25-hydroxyvitamin D2, 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3], 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], and 4β,25-dihydroxyvitamin D3 [4β,25(OH)2D3] in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D2 (n = 28) or vitamin D3 (n = 24) over four months. Metabolite-to-parent compound ratios were calculated to estimate hydroxylase activity. Pairwise before vs after comparisons were made to evaluate effects of vitamin D2 and vitamin D3 on metabolism of vitamin D. Mean postsupplementation metabolite-to-parent ratios were then compared between groups. Results Vitamin D2 was less effective than vitamin D3 in elevating total serum 25(OH)D concentration. Vitamin D2 suppressed mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and mean ratios of 25(OH)D3 to D3 and 1α,25(OH)2D3 to 25(OH)D3, while increasing the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Vitamin D3 increased mean four-month serum concentrations of 25(OH)D3, 24R,25(OH)2D3, 1α,25(OH)2D3, and 4β,25(OH)2D3 and the mean ratio of 24R,25(OH)2D3 to 25(OH)D3. Participants receiving vitamin D2 had lower mean postsupplementation ratios of 25(OH)D3 to vitamin D3 and 1α,25(OH)2D3 to 25(OH)D3 than those receiving vitamin D3. Mean postsupplementation ratios of 24R,25(OH)2D3 to 25(OH)D3 and 4β,25(OH)2D3 to 25(OH)D3 did not differ between groups. Conclusions Bolus-dose vitamin D2 is less effective than bolus-dose vitamin D3 in elevating total serum 25(OH)D concentration. Administration of vitamin D2 reduces 25-hydroxylation of vitamin D3 and 1-α hydroxylation of 25(OH)D3, while increasing 24R-hydroxylation of 25(OH)D3.


Author(s):  
Bridger Singer ◽  
Ryan W Stevens ◽  
Benjamin P Westley ◽  
David P Nicolau

Abstract Purpose A case of vancomycin enzyme immunoassay (EIA) interference confirmed by high-performance liquid chromatography (HPLC) is described. Summary Therapeutic drug monitoring is standard of practice in vancomycin dosing and monitoring in order to maximize the pharmacodynamic effects and minimize toxicity. After a 52-year-old woman received 5 doses of vancomycin, serum concentrations continued to rise for several days in the absence of ongoing vancomycin administration. Despite persistently elevated vancomycin concentrations, the patient clinically deteriorated and required treatment with an alternative agent. Subsequently, serum concentrations were processed via HPLC and analyzed for percent protein binding. Confirmatory analysis revealed substantially lower concentrations by HPLC than were obtained by EIA and an abnormal elevation in protein binding. After discharge from the index admission, the patient returned 11 months later and had a dectectable vancomycin concentration by EIA prior to receipt of vancomycin. HPLC analysis confirmed the true concentration was undetectable. Though the exact interfering substance was not identified, the above discrepancy in concentrations between the two assay methods indicates the presence of assay interference, and adds to the available literature suggesting similar occurrences. This case is particularly troubling given that the level of interference was not such that it would lead a clinician to immediately suspect interference, and the patient experienced treatment failure. Conclusion Falsely elevated values for serum vancomycin concentration, measured by EIA, contributed to treatment failure in a patient. The substance presumably responsible for EIA interferences was not identified.


1996 ◽  
Vol 30 (5) ◽  
pp. 443-448 ◽  
Author(s):  
Susan J Markowsky ◽  
Debra J Skaar ◽  
Joan M Christie ◽  
Steven D Eyer ◽  
David J Ehresman

OBJECTIVE: TO longitudinally evaluate unbound and total serum Phenytoin concentrations during intravenous phenytoin maintenance dosage and to determine the relationship among phenytoin protein binding, serum albumin, and unbound fatty acid concentrations in patients with head injuries during intensive care unit (ICU) and convalescent care. DESIGN: Serum albumin and phenytoin unbound fraction were determined twice weekly during ICU and convalescent care in 10 patients receiving phenytoin following acute brain injury. Phenytoin protein binding was also determined in 10 healthy control subjects. MAIN OUTCOME MEASURES: Longitudinal serum phenytoin concentrations associated with dosage adjustments targeted to achieve unbound phenytoin serum concentrations between 1.0 and 2.0 mg/L were documented during ICU and convalescent care. Longitudinal phenytoin protein binding was correlated with serum albumin and unbound fatty acid concentrations in neurotrauma patients. RESULTS: ICU patients received intravenous therapy for a mean of 15.0 days. The mean ± SD initial phenytoin intravenous dosage regimen of 6.0 ± 0.7 mg/kg/d resulted in mean ± SD total and unbound phenytoin concentrations of 3.2 ± 2.3 and 0.3 ± 0.2 mg/L. Two patients had seizures associated with low phenytoin concentrations. Four patients continued to receive oral phenytoin therapy during convalescent care; phenytoin dosage requirements decreased over time in these patients. During acute and convalescent care, the phenytoin unbound fraction ranged from 6.0% to 18.3% and correlated with albumin (r2 = 0.61, p < 0.0001) but did not correlate with unbound fatty acid concentrations. The mean phenytoin unbound fraction was 10.1% and 8.9% for the ICU and convalescent patients with brain injuries, respectively, and was 7.0% for the healthy volunteers. CONCLUSIONS: Phenytoin protein binding was significantly correlated with albumin and was more variable in ICU and convalescent patients with brain injuries than in healthy volunteers. The high dosage requirements and subtherapeutic unbound phenytoin concentrations observed during acute care are best explained by increased metabolism. Phenytoin dosage requirements decreased during convalescence.


1973 ◽  
Vol 72 (2) ◽  
pp. 265-271 ◽  
Author(s):  
J. H. Dussault ◽  
D. A. Fisher ◽  
J. T. Nicoloff ◽  
V. V. Row ◽  
R. Volpe

ABSTRACT In order to determine the effect of alterations in binding capacity of thyroxine binding globulin (TBG) on triiodothyronine (T3) metabolism, studies were conducted in 10 patients with idiopathically low (7 subjects) or elevated (3 subjects) TBG levels and 10 subjects given norethandrolone (7 male subjects) or oestrogen (3 female subjects). Measurements of serum thyroxine (T4) concentration, maximal T4 binding capacity, serum T3 concentration and per cent dialyzable T3 were conducted. Serum T3 was measured both by chemical and radioimmunoassay methods. In patients with idiopathically low TBG, the mean serum T4 concentration was low (2.4 μg/100 ml), the mean serum T3 level low (55 ng/100 ml), the mean per cent dialyzable T3 increased (0.52%), and the calculated free T3 concentration normal (186 pg/100 ml). In patients with idiopathically high TBG levels the mean T4 concentration was high (10.3 μg/100 ml), the mean T3 level slightly elevated (127 ng/100 ml), the% dialyzable T3 low (0.10%) and the calculated free T3 concentration low normal (123 pg/100 ml). The correlation coefficient between the per cent dialyzable T3 and maximal TBG binding capacity in the 20 subjects was 0.68, a value significant at the P < 0.01 level. Thus, alterations in binding capacity of TBG seem to influence T3 and T4 metabolism similarly; the inverse relationship between the % of dialyzable hormone and total hormone concentration tends to keep the absolue levels of free hormones stable.


Author(s):  
O-Sung Lee ◽  
Jangyun Lee ◽  
Myung Chul Lee ◽  
Hyuk-Soo Han

AbstractThe posterior tibial slope (PTS) is usually adjusted by less than 5 degrees, without considering its individual difference, during posterior cruciate-substituting (PS) total knee arthroplasty (TKA). The effect of these individual changes of PTS would be important because clinical results depending on postoperative PTS were reported conflictingly. We investigated the effect of the change in PTS on the postoperative range of motion (ROM) and clinical scores after PS TKA. We retrospectively reviewed 164 knees from 107 patients who underwent PS TKA with a 2-year follow-up. We analyzed the preoperative and postoperative PTS, ROM, visual analog scale pain scale, Western Ontario and McMaster University Index (WOMAC), Hospital for Special Surgery Knee Score, Knee Society Score, and Forgotten Joint Score (FJS). The association of the absolute change in PTS with ROM and clinical scores was analyzed using correlation analysis and multiple regression analysis. As a result, the mean PTS and mean ROM changed from 9.6 ±  3.4 and 120.1 ±  15.4 degrees preoperatively to 2.0 ±  1.3 and 128.4 ±  9.3 degrees postoperatively, and the mean PTS change was 7.6 ±  3.5 degrees. The PTS change had no statistically significant association with the postoperative ROM and clinical scoring systems, although it did have a weak positive correlation with WOMAC function, No 10 (difficulty in rising from sitting) (correlation coefficient = 0.342, p = 0.041), and moderate positive correlation with the FJS, No. 6 (awareness when climbing stairs) (correlation coefficient = 0.470, p = 0.001). The authors concluded that the amount of change in PTS did not affect the postoperative ROM and clinical scores, although proximal tibial resection with a constant target of PTS resulted in individually different changes in the PTS after PS TKA,


1984 ◽  
Vol 61 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Dennis E. Coyle ◽  
Donald D. Denson ◽  
Gary A. Thompson ◽  
Jane A. Myers ◽  
G. Richard Arthur ◽  
...  

1923 ◽  
Vol 22 (2) ◽  
pp. 123-155 ◽  
Author(s):  
J. Graham Forbes

1. The bacterial content of the air of the Underground Railways, when the average of all results of the bacteriological investigations is taken, does not numerically compare unfavourably with the outside air of London.2. The ratio of the number of organisms growing at room temperature appears to be about 14 for railway air to 10 outside air. For those growing at body temperature the ratio is considerably higher, namely 2 to 1 respectively. The mean per litre, for room temperature organisms, is about 9 in railway air, 6·3 in the outside air; for body temperature organisms 4·6 for railway air, 2·2 for outside air.3. The bacterial content of platform air, except on the City and South London Railway, would appear to be higher than that of carriage air; the total mean for platform air being 52 and for carriage air 42·8 organisms per 5 litres, or a ratio of 16·4 and 13·5 respectively to 10 of the open air. The higher proportion in platform air is generally speaking to be accounted for by the greater amount of draught and dust disturbance.4. The ratios of the total bacterial content of railway carriage air and carriage and platform air on the six lines to open air are estimated in the following proportions:


1993 ◽  
Vol 28 (3) ◽  
pp. 259-264 ◽  
Author(s):  
R. Zordan ◽  
R. Padrini ◽  
V. Bernini ◽  
D. Piovan ◽  
M. Ferrari

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