Comparison of fitting methods for the analysis of plasma concentration-time data resulting from constant rate intravenous infusion

1985 ◽  
Vol 6 (3) ◽  
pp. 313-323
Author(s):  
Stephen L. Johnson ◽  
Michael Mayersohn
Keyword(s):  
Plasma Concentration ◽  
Intravenous Infusion ◽  
Time Data ◽  
Concentration Time ◽  
Constant Rate

scholarly journals Daptomycin Pharmacokinetics in Adult Oncology Patients with Neutropenic Fever

2008 ◽  
Vol 53 (2) ◽  
pp. 428-434 ◽  
Author(s):  
Joseph S. Bubalo ◽  
Myrna Y. Munar ◽  
Ganesh Cherala ◽  
Brandon Hayes-Lattin ◽  
Richard Maziarz
Keyword(s):  
Median Time ◽  
Intravenous Infusion ◽  
Plasma Concentrations ◽  
Neutropenic Fever ◽  
Time Data ◽  
Bacteriostatic Effect ◽  
Oncology Patients ◽  
Time Zero ◽  
Concentration Time ◽  
Free Plasma

ABSTRACT Daptomycin is the first antibacterial agent of the cyclic lipopeptides with in vitro bactericidal activity against gram-positive organisms, including vancomycin-resistant enterococci, methicillin-resistant staphylococci, and glycopeptide-resistant Staphylococcus aureus. The pharmacokinetics of daptomycin were determined in 29 adult oncology patients with neutropenic fever. Serial blood samples were drawn at 0, 0.5, 1, 2, 4, 8, 12, and 24 h after the initial intravenous infusion of 6 mg/kg of body weight daptomycin. Daptomycin total and free plasma concentrations were determined by high-pressure liquid chromatography. Concentration-time data were analyzed by noncompartmental methods. The results (presented as means ± standard deviations and ranges, unless indicated otherwise) were as follows: the maximum concentration of drug in plasma (C max) was 49.04 ± 12.42 μg/ml (range, 21.54 to 75.20 μg/ml), the 24-h plasma concentration was 6.48 ± 5.31 μg/ml (range, 1.48 to 29.26 μg/ml), the area under the concentration-time curve (AUC) from time zero to infinity was 521.37 ± 523.53 μg·h/ml (range, 164.64 to 3155.11 μg·h/ml), the volume of distribution at steady state was 0.18 ± 0.05 liters/kg (range, 0.13 to 0.36 liters/kg), the clearance was 15.04 ± 6.09 ml/h/kg (range, 1.90 to 34.76 ml/h/kg), the half-life was 11.34 ± 14.15 h (range, 5.17 to 83.92 h), the mean residence time was 15.67 ± 20.66 h (range, 7.00 to 121.73 h), and the median time to C max was 0.6 h (range, 0.5 to 2.5 h). The fraction unbound in the plasma was 0.06 ± 0.02. All patients achieved C max/MIC and AUC from time zero to 24 h (AUC0-24)/MIC ratios for a bacteriostatic effect against Streptococcus pneumoniae. Twenty-seven patients (93%) achieved a C max/MIC ratio for a bacteriostatic effect against S. aureus, and 28 patients (97%) achieved an AUC0-24/MIC ratio for a bacteriostatic effect against S. aureus. Free plasma daptomycin concentrations were above the MIC for 50 to 100% of the dosing interval in 100% of patients for S. pneumoniae and 90% of patients for S. aureus. The median time to defervescence was 3 days from the start of daptomycin therapy. In summary, a 6-mg/kg intravenous infusion of daptomycin every 24 h was effective and well tolerated in neutropenic cancer patients.

scholarly journals Vitamin K absorption and kinetics in human subjects after consumption of13C-labelled phylloquinone from kale

2010 ◽  
Vol 104 (6) ◽  
pp. 858-862 ◽  
Author(s):  
Janet A. Novotny ◽  
Anne C. Kurilich ◽  
Steven J. Britz ◽  
David J. Baer ◽  
Beverly A. Clevidence
Keyword(s):  
Plasma Concentration ◽  
Detection Limit ◽  
Vitamin K ◽  
Peak Plasma ◽  
Human Subjects ◽  
Peak Plasma Concentration ◽  
Plasma Samples ◽  
Time Data ◽  
Compartmental Modelling ◽  
Concentration Time

The absorption and plasma disappearance of vitamin K were investigated by uniformly labelling phylloquinone in kale with carbon-13, and by feeding the kale to study subjects. Seven healthy volunteers ingested a single 400 g serving of kale with 30 g vegetable oil. The kale provided 156 nmol of phylloquinone. Serial plasma samples were collected and analysed for the appearance of13C-phylloquinone by HPLC–MS. Six of the subjects showed significant amounts of labelled phylloquinone in plasma, though one subject's plasma was not consistently enriched above the detection limit, and this subject's baseline plasma phylloquinone level was the lowest in the group. After ingestion of the labelled kale, plasma13C-phylloquinone concentration increased rapidly to a peak between 6 and 10 h, and then rapidly decreased. Average peak plasma concentration for the six subjects with detectable13C-phylloquinone was 2·1 nmol/l. Plasma concentration–time data were analysed by compartmental modelling. Modelling results demonstrated a mean (n6) bioavailability of phylloquinone from kale to be 4·7 %. Plasma and tissue half-times for phylloquinone were found to be 8·8 and 215 h, respectively.

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