Cassette Dosing for Pharmacokinetic Screening in Drug Discovery: Comparison of Clearance, Volume of Distribution, Half-Life, Mean Residence Time, and Oral Bioavailability Obtained by Cassette and Discrete Dosing in Rats

2011 ◽  
Vol 100 (9) ◽  
pp. 3862-3874 ◽  
Author(s):  
Rakesh Nagilla ◽  
Melanie Nord ◽  
Jeff J. Mcatee ◽  
Larry J. Jolivette
Keyword(s):  
Drug Discovery ◽  
Residence Time ◽  
Mean Residence Time ◽  
Oral Bioavailability ◽  
Half Life ◽  
Volume Of Distribution ◽  
Pharmacokinetic Screening ◽  
Cassette Dosing

scholarly journals Sialylation on O-linked glycans protects von Willebrand factor from macrophage galactose lectin mediated clearance

Haematologica ◽  
2021 ◽  
Author(s):  
Soracha E. Ward ◽  
Jamie M. O’Sullivan ◽  
Alan B. Moran ◽  
Daniel I. R. Spencer ◽  
Richard A. Gardner ◽  
...  
Keyword(s):  
Residence Time ◽  
Von Willebrand Factor ◽  
Mean Residence Time ◽  
Half Life ◽  
Fold Increase ◽  
Von Willebrand ◽  
Willebrand Factor

Terminal sialylation determines plasma VWF half-life. A role for macrophage galactose lectin (MGL) in regulating hyposialylated VWF clearance has recently been proposed. In this study, we show that MGL influences physiological plasma VWF clearance. MGL inhibition was associated with a significantly extended mean residence time and 3-fold increase in endogenous plasma VWF:Ag levels (p

Rapid Methylprednisolone Clearance in a Patient with Cystic Fibrosis

1988 ◽  
Vol 22 (11) ◽  
pp. 876-878
Author(s):  
Christopher G. Green ◽  
Connie K. Kraus ◽  
Robert F. Lemanske ◽  
Philip M. Farrell ◽  
William J. Jusko
Keyword(s):  
Cystic Fibrosis ◽  
Young Adults ◽  
Oral Bioavailability ◽  
Half Life ◽  
Volume Of Distribution ◽  
Pharmacokinetic Investigation

A pharmacokinetic investigation of administered corticosteroids was conducted in a 16-year-old girl with cystic fibrosis (CF). Equivalent doses of methylprednisolone were given orally and intravenously on consecutive days. Oral bioavailability was essentially 100 percent, ruling out impaired absorption. Drug half-life was shorter and both clearance and volume of distribution were greater in this patient than in normal young adults. From one patient it is impossible to conclude that this unusual disposition of corticosteroids is characteristic of CF. Given the interest in use of corticosteroids in this population, and the examples of other drugs with altered pharmacokinetics in patients with CF, further investigation is warranted.

scholarly journals Toxicokinetics of cotyledoside following intravenous administration to sheep

2003 ◽  
Vol 74 (1) ◽  
Author(s):  
C.J. Botha ◽  
T. Rundberget ◽  
G.E. Swan ◽  
M.S.G. Mulders ◽  
A. Flaoyen
Keyword(s):  
Single Dose ◽  
Residence Time ◽  
Mean Residence Time ◽  
Cardiac Glycoside ◽  
Compartmental Model ◽  
Small Volume ◽  
Volume Of Distribution ◽  
Rapid Decline ◽  
Time Intervals ◽  
Rapid Clearance

Cotyledoside, a bufadienolide cardiac glycoside, was administered intravenously to sheep in 2 studies. In experiment 1, sheep (n = 4) received 0.0135 mg / kg daily on 5 consecutive days and in the 2nd experiment, sheep (n = 4) received 0.027 mg / kg as a single dose. Jugular blood was collected at different time intervals and kinetic parameters were determined. The data fitted a 1-compartmental model. In both experiments a short half-life (t1/2) and mean residence time (MRT), a relative small volume of distribution (Vdss) and rapid clearance were calculated. In the 1st experiment, t1/2 and MRT increased significantly (P < 0.007) from Day (D) 0 to D 4. It is suggested that the rapid decline in plasma cotyledoside concentrations in sheep denotes rapid distribution of cotyledoside to the tissues or extracellular spaces and possible accumulation at the biophase.

scholarly journals Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Mohamed Aboubakr ◽  
Ahmed Soliman
Keyword(s):  
Serum Concentration ◽  
Oral Administration ◽  
Residence Time ◽  
Mean Residence Time ◽  
Half Life ◽  
Pharmacokinetic Profile ◽  
Total Clearance ◽  
Elimination Half ◽  
Muscovy Ducks ◽  
Intravenous And Oral Administration

The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV) and oral (PO) dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t1/2(β)) and mean residence time (MRT) were longer in renal damaged ducks than in healthy ones. Total clearance(Cltot)in renal damaged ducks (0.20 L kg−1 h−1) was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1). Following PO administration, the peak serum concentration(Cmax)was higher in renal damaged than in healthy ducks and was achieved at maximum time(tmax)of 2.47 and 2.05 h, respectively. The drug was eliminated (t1/2(el)) at a significant slower rate (3.94 h) in renal damaged than in healthy ducks (2.89 h). The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values forCmax/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.

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