[Drug metabolism in the septic liver: conclusions about the pharmacokinetics of chloramphenicol].
In nine patients in anaerobic septic shock, five of them with hepatic injury compatible with sepsis liver failure, hematic chloramphenicol concentration was determined at 5 minutes, 1, 2, 3 and 6 hours after intravenous administration of the first of three daily dose (50 mg/k/day); in the hepatic failure group the procedure was repeated with the next dose, previous attempt of haemodynamic compensation with two hours dopamine (3-10 mcg/k/min.) infusion. Starting from experimental data computation adjustment of time-concentration curve and lineal regression with a p = 0.0001 adjustment was done, determining half live (HL), distribution volume (DV), constant of elimination (K) and clearance (CL). In septic shock without hepatic injury patient group, there was noticed a uniform behavior in time-concentration graphic, withdrawn from chloramphenicol bone-marrow depression levels and pharmacokinetics parameters quite near the normal ones, with a reasonable extension of (DV). When attempting hepatic injury patient group, though an individual variability, drug concentration reach bone marrow depression levels and there was a significant lowering of Cl (p = 0.001) and a reasonable one of DV. Dopamine haemodynamic compensation attempt results in an increase of chloramphenicol hematic concentration in the sepsis liver group and the pharmacokinetics levels bear new deterioration. Practical meaning of the methodology used in drug handling in severe hepatic failure is stressed, to allow mathematic valuation of different pathogenic compounds. Though each patient should be individually evaluated, in septic shock without liver injury chloramphenicol dosification should not been any changes but in presence of sepsis liver doses should be diminished to half and administration interval extended to 11.5 hours.
D002701:Chloramphenicol / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D012044:Regression Analysis; D012772:Shock, Septic / Q000378:metabolism*
D002701:Chloramphenicol
Metabolismo de drogas en el hígado de sepsis: conclusiones acerca de la farmacocinética del cloramfenicol.