Joseph N. Miceli

Pharmacokinetics of chloramphenicol and chloramphenicol succinate in infants and children

The metabolism and elimination of chloramphenicol-3-monosuccinate was studied in 45 infants and children, ages 3 days to 16 years, during intravenous administration. The apparent half-life of chloramphenicol was extremely variable, ranging from 1.7 to 12.0 hours with a mean of 5.1 hours. Apparent half-lives were inversely correlated with age. Chloramphenicol-S serum concentration declined biexponentially in most patients, with an estimated mean initial half-life of 0.7 hours and a subsequent longer mean half-life of 2.2 hours. Chloramphenicol-S persisted in serum up to six hours after a dose, and comprised a significantly larger fraction of total chloramphenicol in the serum of infants under one month of age than in older infants and children. A widely variable fraction of the administered chloramphenicol-S dose, with a mean of 33%, was excreted in the urine unchanged and was, therefore, not bioavailable in active form. Mean renal clearance of chloramphenicol-S was 259.5 ml/minute/1.73 M2, four times the mean creatinine clearance, indicating active tubular secretion. Variable hydrolysis and renal elimination of nonhydrolyzed chloramphenicol-S reduces the bioavailability of the antibiotic and appears to contribute substantially to the wide variation in apparent half-life and poor correlation between dose and serum concentration of free chloramphenicol.

Tissue distribution and elimination kinetics of poly-brominated biphenyls (PBB) from rat tissue

The concentration of polybrominated biphenyl (PBB) in serum in a large number of organs was determined in a population of rats for 36 weeks a single dose of PBB. Groups were killed at 6, 12, 24 and 36 weeks after exposure to PBB (1 mg/100g body wt, i.p.). Growth, weight gain and appearance of the rats and their internal organs were normal. Complex and varied relationships were found in tissue concentrations with time after PBB administration. Serum and fat had apparent first-order elimination kinetics with calculated half-times of 23.1 and 69.3 weeks, respectively. For five other tissues, apparent t 1/2s ranged from 9.0-63 weeks, while for four others, kinetics could not be determined from these 4 time points. It is likely that a substantial residue of PBB will still remain in the body of the rat at the end of its life span because of the persistence of PBB in lipid-rich tissues (adipose, adrenal, and brain).

A Therapeutic Approach to the Acutely Overdosed Patient

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Peritoneal Dialysis of Theophylline

The use of peritoneal dialysis as an adjunct to management of theophylline intoxication is presented. Due to the nature of the case, detailed pharmacokinetic explanation was not possible. The data indicate that appreciable quantities of theophylline can be removed using peritoneal dialysis.

Determination of Ticarcillin in Serum by Reversed Phase High Performance Liquid Chromatography

Abstract Ticarcillin is a semi-synthetic penicillin useful against several Pseudomonas species. In order to easily quantitate this drug, a new procedure was developed whereby ticarcillin in serum is converted to its free acid form by the addition of citric acid and, subsequently, extracted into ethyl acetate. The organic extract which contains the nonionized form of ticarcillin is dried under nitrogen, the sample is reconstituted with mobile phase and analyzed by high performance liquid chromatography. Elution is completed in less than five minutes. The assay is linear from 1 mg/L through 100 mg/L. The correlation coefficient of ticarcillin concentration to peak area (r) was 0. 999 over this concentration range. The small sample volume (100 yl) makes this assay particularly suitable for pediatric patients.