Biomedical subjects

C Fiset

Publications and source records attributed to C Fiset.

21 records · Page 2Linked to original sources

PubMed1986

Pharmacokinetics and pharmacodynamics of ciprofloxacin in cystic fibrosis patients.

The pharmacokinetics and blister fluid penetration of oral ciprofloxacin were compared in 11 cystic fibrosis (CF) patients who had sputum colonization but were asymptomatic and in 12 healthy volunteers after a single dose (500 mg) and at steady state (500 mg every 8 h). The antibacterial effect of ciprofloxacin therapy was also evaluated by bacterial counts of colonizing pathogens in the respiratory secretions of CF patients. The CF patients were 15.9% lighter in weight than the controls (P less than 0.05). After a single dose, the elimination half-life of ciprofloxacin was decreased by a third in the CF patients as compared with the controls (2.62 versus 3.93 h, respectively; P less than 0.01). This was the result of a diminished apparent volume of distribution in CF subjects. Interestingly, we observed no statistically significant difference in total apparent and renal clearances between the groups. Suction-induced blister fluid penetration was not different between CF patients and healthy volunteers. In CF patients, ciprofloxacin exhibited levels in respiratory secretions above the reported MIC for Pseudomonas aeruginosa: 1.36 and 1.86 micrograms/ml at 2 h after a single dose and at steady state, respectively. An important fall (mean, 3.9 log10/ml) in the log titer in 10 patients with P. aeruginosa in their respiratory secretions was observed after 5 days of treatment. However, this improvement was short-lived; the secondary increase in bacterial counts observed in five patients and the development of five resistant strains were causes for concern. The pharmacokinetic results presented here showed that ciprofloxacin should be administered every 8 or even every 6 h in CF patients.

Adult↗

PubMed1986

Protein binding of ceftriaxone: comparison of three techniques of determination and the effect of 2-hydroxybenzoylglycine, a drug-binding inhibitor in uremia.

Ceftriaxone is a third-generation cephalosporin exhibiting a long half-life and a concentration-dependent protein binding. This study compared three techniques of protein binding determination (equilibrium dialysis chamber, ultrafiltration cones (Centriflo), and ultrafiltration (Centrifree micro-partition system) on human plasma and serum at ceftriaxone concentrations achieved clinically. A second objective was to determine the effect of 2-hydroxybenzoylglycine (HBG) on the protein binding of ceftriaxone. High performance liquid chromatography (HPLC) and liquid scintillation counting assays were used. Equilibrium dialysis was rotated for 12 h. The supplier's recommendations were followed for ultrafiltration techniques. The plasma protein binding of ceftriaxone, as determined by equilibrium dialysis and assayed by HPLC, decreased from 98.6 to 73.5% for drug concentrations varying from 25 to 400 micrograms/ml. Somewhat lower values were obtained with Centrifree, the binding fell from 92.1 to 73.5% for the same concentration range. Serum protein binding was similar to results obtained with plasma samples. Centriflo cones yielded more inconsistent results. A significant difference was seen between the three techniques (p less than 0.0001, three-way analysis of variance). The addition of HBG, a compound that inhibits drug binding in uremia, resulted in ceftriaxone binding defects similar to those seen in uremic serum. Although equilibrium dialysis remains a classic method of protein binding determination, Centrifree appears to be a better system.

Adolescent↗

PubMedDate not supplied

Mathematical model of an adult human atrial cell: the role of K+ currents in repolarization.

We have developed a mathematical model of the human atria myocyte based on averaged voltage-clamp data recorded from isolated single myocytes. Our model consists of a Hodgkin-Huxley-type equivalent circuit for the sarcolemma, coupled with a fluid compartment model, which accounts for changes in ionic concentrations in the cytoplasm as well as in the sarcoplasmic reticulum. This formulation can reconstruct action potential data that are representative of recordings from a majority of human atrial cells in our laboratory and therefore provides a biophysically based account of the underlying ionic currents. This work is based in part on a previous model of the rabbit atrial myocyte published by our group and was motivated by differences in some of the repolarizing currents between human and rabbit atrium. We have therefore given particular attention to the sustained outward K+ current (I[sus]), which putatively has a prominent role in determining the duration of the human atrial action potential. Our results demonstrate that the action potential shape during the peak and plateau phases is determined primarily by transient outward K+ current, I(sus) and L-type Ca2+ current (I[Ca,L]) and that the role of I(sus) in the human atrial action potential can be modulated by the baseline sizes of I(Ca,L), I(sus) and the rapid delayed rectifier K+ current. As a result, our simulations suggest that the functional role of I(sus) can depend on the physiological/disease state of the cell.

Action Potentials↗