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F B Cerra

Publications and source records attributed to F B Cerra.

238 records · Page 14Linked to original sources
PubMedDate not supplied

Pharmacokinetic analysis verifies P450 function during in vitro and in vivo application of a bioartificial liver.

Lidocaine is a sensitive substrate for evaluating liver P450 function. In this study, metabolism of lidocaine by xenogeneic hepatocytes in a hollow fiber, bioartificial liver was measured under in vitro conditions (n = 6) and in an anhepatic rabbit model. Animals in the treatment group (n = 6) received hemoperfusion by a bioartificial liver that contained 100 million rat hepatocytes. Other anhepatic rabbits received no hemoperfusion (n = 3) or a bioartificial liver with no cells (n = 3). Lidocaine clearance was 7.0 +/- 0.6 ml/min, and the half-life of lidocaine was 5.6 +/- 0.8 hr under in vitro conditions. Conversion of lidocaine to 3-hydroxy-lidocaine was confirmed in vitro and accounted for 46% of lidocaine elimination in the hepatocyte bioartificial liver. During in vivo application of the bioartificial liver, pharmacokinetic parameters of lidocaine metabolism, including drug half-life and metabolite formation, were significantly improved in anhepatic rabbits. 3-Hydroxy-lidocaine profiles verified the activity of a P450 isozyme expressed preferentially by rat hepatocytes in the bioartificial liver. We conclude that hepatic P450 activity was provided by xenogeneic hepatocytes during in vitro and in vivo applications of a bioartificial liver.

Animals↗
PubMedDate not supplied

Effect of pharmacokinetic sampling methods on aminoglycoside dosing in critically ill surgery patients.

We compared pharmacokinetic parameters derived from three aminoglycoside serum concentration sampling methods and evaluated their effects on recommended aminoglycoside dosing regimens in 60 critically ill surgery patients. Patients had presumed or documented gram-negative sepsis, and had at least 4 aminoglycoside serum concentrations measured. We used a one-compartment model for peak and trough, 3-point series, and 4-point series sampling methods. Dosing regimens were calculated for each patient based on values derived from each method. We found differences in regimens for nearly 50% of patients if either 4- or 3-point series sampling was used to calculate the recommended dosage rather than peak and trough sampling. However, the 3-point method required a clinically significant change in regimen in only 12% of patients compared with 4-point sampling. The variability of all values derived from 3-point sampling were well accounted for by the 4-point method (r2 > 0.80). In addition, we noted significantly greater relative precision for 3-point sampling than peak and trough sampling for estimates of clearance, elimination rate, recommended daily dosage, and recommended dosing frequency. We recommend three optimally timed samples be drawn instead of peak and trough levels in dosing aminoglycosides in critically ill surgery patients.

Adult↗