Serum Piperacillin/Tazobactam Pharmacokinetics in a Morbidly Obese Individual

2007 ◽  
Vol 41 (10) ◽  
pp. 1734-1739 ◽  
Author(s):  
Diane Newman ◽  
Marc H Scheetz ◽  
Oluwadamilola A Adeyemi ◽  
Mauro Montevecchi ◽  
David P Nicolau ◽  
...  
Keyword(s):  
Steady State ◽  
Serum Concentration ◽  
Half Life ◽  
Obese Individual ◽  
Morbidly Obese ◽  
Population Pharmacokinetic ◽  
Steady State Concentration ◽  
Data Set ◽  
Peripheral Venous Catheter ◽  
State Concentration

Objective: To report pharmacokinetic alterations and optimal dosing of piperacillin/tazobactam in an obese patient. Case Summary: A 39-year-old morbidly obese (weight 167 kg, body mass index 50 kg/m2) man was treated with piperacillin/tazobactam 3.375 g every 4 hours for recurrent cellulitis. The wound culture grew Groups A and B Streptococcus and rare Pseudomonas aeruginosa. Blood samples were obtained at steady-state from a peripheral venous catheter at 0, 0.5, 1, 2, 3, and 4 hours after the start of the infusion. Population pharmacokinetics were generated from a previously published data set. The serum concentrations of piperacillin/tazobactam obtained in the patient were compared with the 95% confidence interval from the representative population. Pharmacokinetic parameters such as maximal serum concentration, minimal serum concentration, average steady-state concentration, half-life, elimination rate constant, volume of distribution (Vd), clearance, area under the curve at steady-state, and percent of time greater than the minimum inhibitory concentration (%t>MIC) were calculated and qualitatively compared between the sample and the population. Discussion: Substantial differences were noted in both the absolute values at the times of sample collection and the overall concentration-versus-time profile of both compounds. The morbidly obese individual compared with the population demonstrated a reduced average serum steady-state concentration: 39.8 mg/L versus 123.6 mg/L, an increased Vd: 54.3 L versus 12.7 L, and an increased half-life: 1.4 hours versus 0.6 hours, respectively. The %t>MIC of piperacillin for the patient, assuming MICs of 2, 4, 8, 16, 32, 64, and 128 mg/L, was 100%. 100%, 90.9%, 55.4%. 19.9%, 0%, and 0%, respectively. Conclusions: Pathogens with elevated MICs may require altered dosing schemes with piperacillin/tazobactam. Future studies are warranted to assess increased dosages, more frequent dosing intervals, or continuous infusion dosing schemes for obese individuals with serious infections.

Time to Steady State following a Change in Dosing Rate

DICP ◽  
1989 ◽  
Vol 23 (6) ◽  
pp. 468-472 ◽  
Author(s):  
Richard G. D'Angio ◽  
Peter R. Gwilt
Keyword(s):  
Steady State ◽  
Half Life ◽  
Mathematical Proof ◽  
The Body ◽  
Steady State Concentration ◽  
Initial Concentration ◽  
Elimination Half Life ◽  
Drug Concentrations ◽  
Elimination Half ◽  
State Concentration

Drugs administered at fixed intervals or by continuous infusion will accumulate in the body until steady state is achieved. The time to a given percentage of the eventual steady-state concentration has previously been considered to be dependent only on the elimination half-life. This is incorrect. Although the rate of drug accumulation in the body is dependent only on the elimination half-life, the time to a given percentage of steady state is dependent on both the elimination half-life of the drug and the initial concentration. This paper presents the mathematical proof of this concept, computer simulations demonstrating the use of these equations, and nomograms for use in clinical practice. The use of this method allows serum drug concentrations to be evaluated earlier than previously predicted after changes in the dosing rate.

Inadequacy of FDA Dosing Guidelines for Theophylline Use in Neonates

1986 ◽  
Vol 20 (6) ◽  
pp. 481-484 ◽  
Author(s):  
Jamie T. Gilman ◽  
Peter Gal
Keyword(s):  
Steady State ◽  
Serum Concentration ◽  
Oral Therapy ◽  
Loading Dose ◽  
Serum Concentrations ◽  
Steady State Concentration ◽  
Significant Difference ◽  
Postconceptional Age ◽  
State Concentration

The efficacy of the FDA guidelines for theophylline dosing in newborns was evaluated retrospectively in 224 patients who had clearance data available. Mean projected post loading dose serum concentration was 4.1 ± 1.0 mg/L in 160 patients. Mean projected steady-state concentration was 4.8 ± 1.6 mg/L in 189 patients receiving intravenous aminophylline and 4.2 ± 1.3 mg/L in 35 patients on oral therapy. Projected serum concentrations were subtherapeutic (<6.0 mg/L) in 181 of the 224 patients analyzed. There was a statistically significant difference in serum concentrations between asphyxiated and nonasphyxiated patients (p<0.001). There was no significant difference in mean projected serum concentrations between patients age 26–41 weeks (postconceptional age). This study suggests that the FDA dosing guidelines for theophylline in infants is inadequate and results in subtherapeutic (<6.0 mg/L) serum concentrations in the majority of newborns.

scholarly journals Factors affecting the mixed-layer concentrations of singlet oxygen in sunlit lakes

2021 ◽  
Author(s):  
Sarah Bonnie Partanen ◽  
Jennifer N. Apell ◽  
Jianming Lin ◽  
Kristopher McNeill
Keyword(s):  
Steady State ◽  
Singlet Oxygen ◽  
Mixed Layer ◽  
Half Life ◽  
Environmental Fate ◽  
Steady State Concentration ◽  
Factors Affecting ◽  
Fate Modelling ◽  
State Concentration

The steady-state concentration of singlet oxygen within a lake ([1O2]SS) is an important parameter that can affect the environmental half-life of pollutants and environmental fate modelling. However, values of [1O2]SS...

scholarly journals Manganese accumulation in bone following chronic exposure in rats: Steady-state concentration and half-life in bone

2014 ◽  
Vol 229 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Stefanie L. O’Neal ◽  
Lan Hong ◽  
Sherleen Fu ◽  
Wendy Jiang ◽  
Alexander Jones ◽  
...  
Keyword(s):  
Steady State ◽  
Half Life ◽  
Chronic Exposure ◽  
Steady State Concentration ◽  
State Concentration

Divergent effects of intravenous GSH and cysteine on renal and hepatic GSH

1992 ◽  
Vol 263 (2) ◽  
pp. R348-R352 ◽  
Author(s):  
S. Aebi ◽  
B. H. Lauterburg
Keyword(s):  
Steady State ◽  
De Novo ◽  
Feedback Inhibition ◽  
Therapeutic Use ◽  
Steady State Concentration ◽  
De Novo Synthesis ◽  
State Concentration ◽  
Cellular Thiol

There is a growing interest in the therapeutic use of sulfhydryls. To assess the effect of glutathione (GSH) and cysteine on the cellular thiol status, thiols were administered intravenously to rats in doses ranging from 1.67 to 8.35 mmol/kg with and without pretreatment with 4 mmol/kg buthionine-[S,R]-sulfoximine (BSO), an inhibitor of GSH synthesis. One hour after administration of 1.67 mmol/kg GSH, the concentration of GSH rose from 5.2 +/- 1.0 to 8.4 +/- 0.9 mumol/g and from 2.5 +/- 0.5 to 3.7 +/- 0.7 mumol/g in liver and kidneys, respectively. After 8.35 mmol/kg, hepatic GSH did not increase further, but renal GSH rose to 6.7 +/- 1.8 mumol/g. Infusion of cysteine increased hepatic GSH to the same extent as intravenous GSH, but renal GSH did not increase after 1.67 mmol/kg and even significantly decreased to 0.6 +/- 0.2 mumol/g after 8.35 mmol/kg. In the presence of BSO, GSH resulted in a significant increase in renal but not hepatic GSH, suggesting that the kidneys take up intact GSH and indicating that the increment in hepatic GSH was due to de novo synthesis. The present data show that hepatic GSH can be markedly increased in vivo by increasing the supply of cysteine. Measurements of hepatic cysteine indicate that up to a concentration of approximately 0.5 mumol/g cysteine is a key determinant of hepatic GSH, such that the physiological steady-state concentration of GSH in the liver appears to be mainly determined by the availability of cysteine. At higher concentrations GSH does not increase further, possibly due to feedback inhibition of GSH synthesis or increased efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of oxidative stress during imbibition of soybean embryonic axes

1994 ◽  
Vol 102 ◽  
pp. 279-286 ◽  
Author(s):  
Susana Puntarulo
Keyword(s):  
Oxidative Stress ◽  
Steady State ◽  
External Medium ◽  
Tocopherol Content ◽  
Active Species ◽  
Oxygen Species ◽  
Steady State Concentration ◽  
Embryonic Axes ◽  
State Concentration

SynopsisBoth respiration and generation by soybean embryonic axes showed a sharp increase upon germination, leading to a significant increase in the steady-state concentration of and H2O2 after 6 h of imbibition. An assay was developed to assess in vivo generation of reactive oxygen species, based upon DCFH-DA oxidation. Fluorescence of the external medium was dependent on reaction time and axes number and was inhibited by catalase.α-Tocopherol content declined significantly after 24 h of incubation, as compared to the content at the onset of germination. Incubation in the presence of redox cycling agent paraquat (4 mM) for 24 h increased α-tocopherol content to 1.9±0.2 nmol per axis from 1.0 ± 0.1 nmol per axis in the absence of paraquat. Supplementation of the incubation medium with 500 μM Fe-EDTA increased α-tocopherol content to 1.8±0.1 nmol/axis and DCFH-DA oxidation by two-fold.The data presented here showed that active metabolism at the onset of germination increased steady-state concentration of oxygen active species and suggest that cellular content of α-tocopherol is physiologically adjusted as a response to conditions of oxidative stress.

8-Hydroxylation and Glucuronidation of Mirtazapine in Japanese Psychiatric Patients: Significance of the Glucuronidation Pathway of 8-Hydroxy-Mirtazapine

2019 ◽  
Vol 52 (05) ◽  
pp. 237-244
Author(s):  
Masataka Shinozaki ◽  
Jason Pierce ◽  
Yuki Hayashi ◽  
Takashi Watanabe ◽  
Taro Sasaki ◽  
...  
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Plasma Levels ◽  
High Performance ◽  
Psychiatric Patients ◽  
Plasma Concentrations ◽  
Steady State Concentration ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
State Concentration

Abstract Introduction  To investigate the metabolism of mirtazapine (MIR) in Japanese psychiatric patients, we determined the plasma levels of MIR, N-desmethylmirtazapine (DMIR), 8-hydroxy-mirtazapine (8-OH-MIR), mirtazapine glucuronide (MIR-G), and 8-hydroxy-mirtazapine glucuronide (8-OH-MIR-G). Methods  Seventy-nine Japanese psychiatric patients were treated with MIR for 1–8 weeks to achieve a steady-state concentration. Plasma levels of MIR, DMIR, and 8-OH-MIR were determined using high-performance liquid chromatography. Plasma concentrations of MIR-G and 8-OH-MIR-G were determined by total MIR and total 8-OH-MIR (i. e., concentrations after hydrolysis) minus unconjugated MIR and unconjugated 8-OH-MIR, respectively. Polymerase chain reaction was used to determine CYP2D6 genotypes. Results  Plasma levels of 8-OH-MIR were lower than those of MIR and DMIR (median 1.42 nmol/L vs. 92.71 nmol/L and 44.96 nmol/L, respectively). The plasma levels (median) of MIR-G and 8-OH-MIR-G were 75.00 nmol/L and 111.60 nmol/L, giving MIR-G/MIR and 8-OH-MIR-G/8-OH-MIR ratios of 0.92 and 59.50, respectively. Multiple regression analysis revealed that smoking was correlated with the plasma MIR concentration (dose- and body weight–corrected, p=0.040) and that age (years) was significantly correlated with the plasma DMIR concentration (dose- and body weight–corrected, p=0.018). The steady-state plasma concentrations of MIR and its metabolites were unaffected by the number of CYP2D6*5 and CYP2D6*10 alleles. Discussion  The plasma concentration of 8-OH-MIR was as low as 1.42 nmol/L, whereas 8-OH-MIR-G had an approximate 59.50 times higher concentration than 8-OH-MIR, suggesting a significant role for hydroxylation of MIR and its glucuronidation in the Japanese population.

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