colistin and Nephrotic-Syndrome

This review mainly summarizes selected aspects of the present knowledge of drug elimination kinetics independent of developmental changes, with special attention given to clinical situations. The effects of different disease states, drug interactions, changes in urinary pH, induction of microsomal enzymes, competition for renal excretory mechanisms, possible enterohepatic recirculation, binding of drugs to tissues, effects of a drug on another drug's metabolizing organ, and dose-dependent elimination, on increase or decrease of drug elimination rates in children, have been presented. Based on the available data it seems that one may postulate the following conclusions: (1) that the distribution factors as well as changes in drug elimination capacities seem to play a role, perhaps with differing relative importance, during each of the maturational periods; (2) that the physicochemical properties of a drug and its dosage, as well as changes in the volume of distribution in children, in the course of certain disease states may have a significant effect on kinetics of drug disposition in the body; (3) that systemic clearance, a model independent parameter, rather than elimination half-life, a hybrid pharmacokinetic parameter, more accurately reflects elimination of some drugs from the body; (4) that each drug and every clinical situation may require the evaluation of the direct effect on pharmacokinetic processes, since general principles may not always apply; (5) that drug disposition studies should also be performed, if possible, on patients under actual clinical situations and receiving the usual therapeutic regime, and (6) that the half-life of colistin is independent of postnatal age which should serve as a warning not to generalize about drug excretion in the young infant.

Topics: Adult; Anti-Bacterial Agents; Brain Injuries; Child; Child, Preschool; Colistin; Cystic Fibrosis; Digoxin; Dose-Response Relationship, Drug; Drug Interactions; Female; Half-Life; Heart Failure; Humans; Hydrogen-Ion Concentration; Hypothermia, Induced; Infant; Infant, Newborn; Kidney; Kinetics; Liver; Nephrotic Syndrome; Nutrition Disorders; Pharmaceutical Preparations; Phenobarbital; Reye Syndrome; Serum Albumin; Urine

Twenty-one patients who received intravenous colistimethate sodium (CMS) for at least 7 days for the treatment of multidrug-resistant Gram-negative bacterial infections were included in a prospective cohort study at 'Henry Dunant' Hospital in Athens, Greece. The mean (+/- standard deviation) and median daily doses, cumulative doses and duration of treatment of intravenous CMS were, respectively, 5.5 (+/- 1.9) and 6 million IU, 90.2 (+/- 52.0) and 72 million IU, and 17.7 (+/- 11.7) and 15 days (range 7-54 days). Three patients (14.3%) developed nephrotoxicity during treatment with CMS. The cumulative dose of administered CMS was statistically correlated with the difference in values of serum creatinine between the end and start of CMS treatment (r = 0.6, P = 0.004 by Spearman's test).

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Cohort Studies; Colistin; Creatinine; Female; Gram-Negative Bacterial Infections; Greece; Humans; Injections, Intravenous; Kidney Function Tests; Male; Middle Aged; Nephrotic Syndrome; Prospective Studies; Treatment Outcome