Pharmacokinetics of Propylene Glycol in Humans During Multiple Dosing Regimens

1985 ◽  
Vol 74 (8) ◽  
pp. 876-879 ◽  
Author(s):  
Dale K. Yu ◽  
William F. Elmquist ◽  
Ronald J. Sawchuk
Keyword(s):  
Propylene Glycol ◽  
Multiple Dosing ◽  
Dosing Regimens

scholarly journals Computer-controlled in-vitro simulation of multiple dosing regimens

1985 ◽  
Vol 15 (suppl A) ◽  
pp. 169-173 ◽  
Author(s):  
B. Ledergerber ◽  
J. Blaser ◽  
R. Luthy
Keyword(s):  
Multiple Dosing ◽  
Dosing Regimens ◽  
In Vitro Simulation ◽  
Computer Controlled

Stable-Isotope Methodology for the Bioavailability Study of Phenytoin During Multiple-Dosing Regimens

1985 ◽  
Vol 74 (5) ◽  
pp. 503-507 ◽  
Author(s):  
Yasuji Kasuya ◽  
Kumiko Mamada ◽  
Shigeo Baba ◽  
Makoto Matsukura
Keyword(s):  
Stable Isotope ◽  
Multiple Dosing ◽  
Bioavailability Study ◽  
Dosing Regimens

Simultaneous Analysis of the Single and Multiple Dose Pharmacokinetics of the Non-Steroidal Anti-Inflammatory, Alclofenac

1979 ◽  
Vol 7 (4) ◽  
pp. 253-262
Author(s):  
Lawrence T Sennello ◽  
Robert C Sonders ◽  
William G Jochimsen ◽  
Nadav Friedmann
Keyword(s):  
Half Life ◽  
Absorption Rate ◽  
Study Drug ◽  
Compartment Model ◽  
Multiple Dosing ◽  
Healthy Adult Male ◽  
Dosing Regimens ◽  
Rate Of Absorption ◽  
Multiple Dose Pharmacokinetics ◽  
Single Set

Two clinical studies were conducted to study the pharmacokinetics of alclofenac in healthy adult male volunteers when the drug was administered in both single and multiple dosing regimens. The first study involved the participation of thirty-two subjects, each of whom received single 500 mg and 1000 mg oral doses of alclofenac, using a complete crossover experimental design. The second study involved the participation of sixteen subjects, eight of whom received a 500 mg dose, and eight of whom received a 1000 mg dose of alclofenac every eight hours for ninety-six consecutive hours (four days) with no crossover. In the first study, plasma alclofenac levels were monitored for ten hours post-dosing, while in the second study, drug levels were monitored for four and one-half days (i.e. through twelve hours after the last dose). Initially, using the programme NONLIN, single dose data were fit to a bi-exponential equation, with output from these fits serving as initial estimates for a second fit to the same equation. The results of these second fits were then used as initial estimates to fit the multiple dosing data to a multiple dosing one-compartment model with first order absorption and elimination. Finally, all sets of data were simultaneously fit to the one-compartment open model, with both single and multiple dosing, in an attempt to obtain a uniform interpretation, with a single set of parameters that would adequately describe the plasma alclofenac levels to be expected with a variety of dosing regimens. It was found that the kinetics did not significantly change upon going from single to multiple dosing, and that with the exception of the apparent absorption rate constant, a single set of parameters adequately described all the data collected. The rate of absorption seemed to be somewhat dose-dependent at these levels, being slower after 1000 mg doses than after 500 mg doses. For this reason, the simultaneous fitting program was allowed to estimate different absorption rate constants for the 500 mg and 1000 mg doses. The results of these simultaneous analyses were: Vol Distribution/Fraction Abs = 6.56 Litres Absorption Half-Life (500 mg) = 14 Minutes Absorption Half-Life (1000 mg) = 30 Minutes Elimination Half-Life = 2.1 Hours Absorption Lag Time = 14 Minutes

scholarly journals Semimechanistic Pharmacokinetic-Pharmacodynamic Model with Adaptation Development for Time-Kill Experiments of Ciprofloxacin against Pseudomonasaeruginosa

2010 ◽  
Vol 54 (6) ◽  
pp. 2379-2384 ◽  
Author(s):  
Nicolas Grégoire ◽  
Sophie Raherison ◽  
Claire Grignon ◽  
Emmanuelle Comets ◽  
Manuella Marliat ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Fold Increase ◽  
Multidrug Efflux ◽  
Multiple Dosing ◽  
Initial Inoculum ◽  
Dosing Regimens ◽  
Moderate Resistance ◽  
Time Kill

ABSTRACT The objective of this study was to implement a semimechanistic pharmacokinetic-pharmacodynamic (PK-PD) model to describe the effects of ciprofloxacin against Pseudomonas aeruginosa in vitro. Time-kill curves were generated with an initial inoculum close to 5 × 106CFU/ml of P. aeruginosa PAO1 and constant ciprofloxacin concentrations between 0.12 and 4.0 μg/ml (corresponding to 0.5× and 16× MIC). To support the model, phenotypic experiments were conducted with the PAO7H mutant strain, which overexpresses the MexEF OprN efflux pump and phenyl arginine β-naphthylamide (PAβN), a known efflux inhibitor of main Mex multidrug efflux systems. A population approach was used for parameter estimation. At subinhibitory ciprofloxacin concentrations (0.12 and 0.25 μg/ml), an initial CFU decay followed by regrowth was observed, attesting to rapid emergence of bacteria with increased but moderate resistance (8-fold increase of MIC). This phenomenon was mainly due to an overexpression of the Mex protein efflux pumps, as shown by a 16-fold diminution of the MIC in the presence of PAβN in these strains with low-level resistance. A PK-PD model with adaptation development was successfully used to describe these data. However, additional experiments are required to validate the robustness of this model after longer exposure periods and multiple dosing regimens, as well as in vivo.

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