scholarly journals Altered Aminoglycoside Pharmacokinetics in the Critically Ill

1988 ◽  
Vol 16 (4) ◽  
pp. 418-422 ◽  
Author(s):  
M. J. Beckhouse ◽  
I. M. Whyte ◽  
P. L. Byth ◽  
J. C. Napier ◽  
A. J. Smith
Keyword(s):  
Critically Ill ◽  
Compartment Model ◽  
Serum Levels ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Data ◽  
Post Dose ◽  
Apparent Volume Of Distribution ◽  
Trough Levels ◽  
Volumes Of Distribution

We studied prospectively 49 patients being treated in an intensive care unit with aminoglycosides for gram-negative sepsis. Pharmacokinetic data were calculated from three post-dose serum levels using a one-compartment model. Doses required to achieve peak levels between 5 and 10 mg/l with trough levels approximately 1.0 mg/l ranged between 2 and 12 mg/kg per day (mean dose 7 mg/kg per day). During therapy 60% of the patients had a change in their apparent volume of distribution (Vd) of greater than 20%. These patients were likely to have confirmed infection and to be febrile at the start of treatment. Two to three weeks after discharge ten patients were restudied after a single dose of aminoglycoside. There was a reduction in mean Vd from 0.24 to 0.18 l/kg (P < 0.02). Critically ill patients have significantly larger volumes of distribution and may require larger doses per kilogram of body weight of aminoglycoside to achieve therapeutic concentrations. Due to considerable variation in kinetic parameters, the use of standard doses or dosing nomograms is not recommeded.

Letters to the Editor

PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 602-603
Author(s):  
Charles H. Feldman ◽  
Vincent E. Hutchinson ◽  
Charles E. Pippenger ◽  
Thomas A. Blumenfeld ◽  
Bernard R. Feldman ◽  
...  
Keyword(s):  
Elimination Rate ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Apparent Volume ◽  
Systemic Circulation ◽  
Volume Of Distribution ◽  
Letters To The Editor ◽  
Correct Formula ◽  
Original Report ◽  
Apparent Volume Of Distribution

We appreciate the comments of Weinberger et al and Spino et al. The equation utilized in our original report to calculate the apparent volume of distribution (V) was in error, as it was based on determinations for drugs that exhibit monoexponential elimination following a single intravenous dose. The correct formula for oral dosing at steady state with a drug obeying one-compartment model kinetics is: V = F.X0/AUCτ. K, where F is the total fraction of dose reaching systemic circulation, X0, is the dose, AUCτ is the area under the curve during a dosing interval; K is the elimination rate constant.1

Serum Quinidine Levels after Chronic Administration of Four Different Quinidine Formulations

1976 ◽  
Vol 4 (6) ◽  
pp. 393-401 ◽  
Author(s):  
A M Soeterboek ◽  
M Van Thiel
Keyword(s):  
Serum Level ◽  
Chronic Administration ◽  
Serum Levels ◽  
Relative Bioavailability ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Level Curves ◽  
Trough Serum ◽  
Total Body ◽  
Apparent Volume Of Distribution

The serum levels produced by four different quinidine formulations have been studied. The relative bioavailability of the formulations was demonstrated as were the mean peak serum levels and their timing in relation to dosage. From the data obtained, the biological half-lives were measured and the apparent volume of distribution and total body clearance were calculated for each formulation. The generic tablets of quinidine monosulphate from five different manufacturers were not significantly different from each other in any respect and produced the expected peak and trough serum level curves. The serum level curves resulting from administration of quinidine polygalacturonate (Cardioquin®) were not significantly different from those resulting from the generic tablets, and this formulation may be regarded as therapeutically equivalent to the generic formulations. Both sustained-release formulations of quinidine bisulphate, Durettes® and Kiditard® (given at the same dosage) were shown to offer a means whereby, with simple twice-daily dosage, quinidine maintenance treatment may be continued with the confidence that the serum levels may be maintained throughout each 24-hour period without peaks into the toxic levels and troughs into the levels of no effect.

Diet and Theophylline

PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 600-601
Author(s):  
Miles Weinberger ◽  
Gary Smith ◽  
Gary Milavetz
Keyword(s):  
Serum Concentration ◽  
Half Life ◽  
Clinical Relevance ◽  
Recent Article ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Apparent Volume Of Distribution ◽  
Zero Time ◽  
Volumes Of Distribution

The recent article by Feldman et al1 demonstrating the effect of diet on theophylline elimination is qualitatively consistent with a previous report in adults2 but contains quantitative inaccuracies that distort the clinical relevance of the data. Specifically, the apparent volumes of distribution and the half-life of elimination were inappropriately determined, resulting in specious values that are not consistent with the more appropriately calculated clearance values. The authors state that the apparent volume of distribution was calculated by dividing the serum concentration extrapolated to zero time into the dose of the drug.

scholarly journals Changes in Vancomycin Pharmacokinetics in Critically Ill Infants

1995 ◽  
Vol 23 (6) ◽  
pp. 678-682 ◽  
Author(s):  
A. G. S. Gous ◽  
M. D. Dance ◽  
J. Lipman ◽  
D. K. Luyt ◽  
R. Mathivha ◽  
...  
Keyword(s):  
Critically Ill ◽  
Serum Levels ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Routine Monitoring ◽  
Elimination Half ◽  
Change In Mean

We aimed to assess the pharmacokinetics of vancomycin in critically ill infants, and to evaluate the standard recommended dose of 10 mg/kg 6 hourly. All infants admitted to the Baragwanath Hospital ICU who had arterial lines in situ, and for whom vancomycin 10 mg/kg 6 hourly was prescribed for an infective insult and who had parental consent, were included in the study. Vancomycin was infused over 60 minutes. Serum samples were taken immediately before the dose and at 30, 60, 120 and 300 minutes after the end of the vancomycin infusion, on days 2 and 8 of therapy. Extrapolated peak concentration (Cmax), trough concentration (Cmin), apparent volume of distribution (Vd), elimination half-life (t½el) and clearance (CL) were determined for each patient. Day 2 values were compared with those of day 8. Day 2 serum concentrations were assayed on 20 patients and day 8 concentrations in 15. The mean vancomycin Vd on day 2 (0.81 l/kg) was significantly (P=0.007) larger than that on day 8 (0.44 l/kg). The change in Vd resulted in a significant change in mean Cmax (29.1 vs 35.5 μg/ml) (P=0.02) and mean t½el (5.3 vs 3.4h) (P=0.01) over the treatment period. Critically ill infants displayed a large initial volume of distribution which probably resulted from aggressive fluid resuscitation. This also results in a large variation in other pharmacokinetic parameters, namely Cmax and t½el. Although the routine monitoring of vancomycin serum concentrations remain controversial, we feel that in view of these large pharmacokinetic variations, the critically ill infant is a specific group where monitoring of vancomycin serum levels is indicated.

scholarly journals Pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis

2016 ◽  
pp. AAC.01657-16 ◽  
Author(s):  
Danny Tsai ◽  
Penelope Stewart ◽  
Rajendra Goud ◽  
Stephen Gourley ◽  
Saliya Hewagama ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Critically Ill ◽  
Total Body Weight ◽  
Compartment Model ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Population Pharmacokinetic Study

Objectives: There are no available pharmacokinetic data to guide piperacillin dosing in critically ill Australian Indigenous patients despite numerous reported physiological differences. This study aimed to describe the population pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis.Methods: A population pharmacokinetic study of Indigenous patients with severe sepsis was conducted in a remote hospital intensive care unit. Plasma samples were collected over two dosing intervals and assayed by validated chromatography. Population pharmacokinetic modelling was conducted using Pmetrics®.Results: Nine patients were recruited and a two compartment model adequately described the data. Piperacillin clearance (CL), volume of distribution of the central compartment (Vc), distribution rate constant from central to peripheral compartment and from peripheral to central compartment were 5.6 ± 3.2 L/h, 14.5 ± 6.6 L, 1.5 ± 0.4 h-1and 1.8 ± 0.9 h-1respectively, where CL and Vcwere found to be described by creatinine clearance (CrCL) and total body weight respectively.Conclusion: In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CrCL were found to be the most important determinant of piperacillin pharmacokinetics.

scholarly journals The pharmacokinetics of [18F]UCB-H revisited in the healthy non-human primate brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sébastien Goutal ◽  
Martine Guillermier ◽  
Guillaume Becker ◽  
Mylène Gaudin ◽  
Yann Bramoullé ◽  
...  
Keyword(s):  
Slow Component ◽  
Specific Binding ◽  
Compartment Model ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Pharmacokinetic Data ◽  
Limited Information ◽  
Positron Emission ◽  
Human Primate

Abstract Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we evaluate the reliability of the three most commonly used modelling approaches for [18F]UCB-H in the non-human cynomolgus primate, adding the coupled fit of the non-displaceable distribution volume (VND) as an alternative approach to improve unstable fit. The results are discussed in the light of the current state of SV2A PET ligands. Results [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), although the model did not always converge (large total volume of distribution (VT) or large uncertainty of the estimate). 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower specific signal of [18F]UCB-H compared to the newest SV2A-ligands. However, the measures of VND and the influx parameter (K1) are similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50% displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. As previously demonstrated in clinical studies, the graphical method of Logan provided a more robust estimate of VT with only a small bias compared to 2TCM. Conclusions Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.

Pharmacokinetics and Tissue Distribution of Norfloxacin in Eel Following Oral Gavage

2012 ◽  
Vol 452-453 ◽  
pp. 1069-1073
Author(s):  
Yun Hua Hui ◽  
You Qiong Cai ◽  
Bing Feng ◽  
Wen Ruan ◽  
Hui Juan Yu
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
European Eel ◽  
Half Time ◽  
Oral Gavage ◽  
Concentration Time ◽  
Liver And Kidney ◽  
Apparent Volume Of Distribution ◽  
Different Tissues ◽  
Body Clearance

The pharmacokinetics of norfloxacin were investigated in the European eel after a single oral gavage of 10 mg norfloxacin per kg body weight. The concentrations of norfloxacin in the main tissues (kidney, muscle, hepatopancreas and blood) were simultaneously detected by HPLC. All of the concentration-time curves of norfloxacin in the plasma, muscle and liver were consistent with absorption of a two-compartment open kinetic model. Norfloxacin was widely distributed in different tissues in the European eel. Apparent volume of distribution (Vd) was 52.025 L/kg, 34.589 L/kg, 2.795 L/kg, and 0.969 L/kg, in plasma, muscle, liver and kidney, respectively. Norfloxacin in the eel was proved to eliminate slowly, and half-time (tβ1/2) in plasma, muscle, liver and kidney, was 201.222 h, 123.789 h, 120.634 h and 627473.495 h, respectively. Body clearance was 0.689 L / ( kg•h ), 1.793 L/( kg•h ), 0.097 L/( kg•h ) and 0.028 L /( kg•h ), in plasma, muscle, liver and kidney, respectively.

Ketamine kinetics: decerebrate vs. intact cats

1979 ◽  
Vol 57 (8) ◽  
pp. 878-881 ◽  
Author(s):  
James E. Heavner ◽  
Duane C. Bloedow
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Drug Dose ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Peripheral Compartment ◽  
Blood Concentrations ◽  
Open Model ◽  
Apparent Volume Of Distribution ◽  
Compartment Open Model

Pharmacokinetic parameters of a ketamine (10 mg/kg, iv) bolus in decerebrate and intact cats were compared. A two-compartment open model best described the data in both groups. The apparent volume of distribution of the peripheral compartment, the apparent volume of distribution of the drug in the body, and the half-life of the postdistributive phase were significantly less (p < 0.05) in the decerebrate animals. These results emphasize the importance of correlating behavior and neuronal activity with plasma or blood concentrations of drug in animals rather than assuming that, for a given drug dose, blood (and thus tissue) levels of the agent will be similar regardless of how the animal is prepared for study.

Letters to the Editor

PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 601-602
Author(s):  
M. Spino ◽  
J. J. Thiessen ◽  
A. Isles ◽  
H. Levison ◽  
S. M. MacLeod
Keyword(s):  
Clinical Application ◽  
Drug Concentration ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Single Intravenous Dose ◽  
Letters To The Editor ◽  
Potential Clinical Application ◽  
Apparent Volume Of Distribution

We found the report by Feldman et al1 interesting with potential clinical application. However, we would like to point out an error in their determination of the apparent volume of distribution (V) and comment on both their methodology and results. They state that V was calculated by dividing the dose of the drug by the extrapolated y intercept for drug concentration at time 0. This method is correct for a drug which exhibits monoexponential elimination following a single intravenous dose.

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