Bioavailability and clearance of chloramphenicol after intravenous chloramphenicol succinate.
Bioavailability of chloramphenicol and kinetics of chloramphenicol succinate and chloramphenicol were studied in 12 patients. Chloramphenicol succinate, 25 mg/kg, was injected intravenously every 6 hr over 0.5 to 1 hr. Both the drug and the prodrug were analyzed by high-pressure liquid chromatography. Bioabailability of chlorampenicol ranged from 0.55 to 0.92 and total, renal, and nonrenal clearance from 6.81 to 98.22, 2.54 to 26.90, and 3.73 to 87.38 ml/m2/min, while clearances of chloramphenicol succinate ranged from 84.75 to 916.00 28.40 to 312.00, and 26.06 to 760.93 ml/m2/min. Urinary recovery of chloramphenicol was 3% to 25% and that of chloramphenicol succinate was 7% to 45%. Mean apparent volumes of distribution were 0.71 l/kg for chloramphenicol and 2.10 l/kg for chloramphenicol succinate and elimination half-lifes were 4.03 and 2.65 hr, respecitively. There were relationships between patient age and clearance of both drugs. Incomplete bioavailability of chloramphenicol and the more than 10-fold variability in clearance of both chloramphenicol and chloramphenicol succinate explain the need for individualizing doses to achieve thrapeutic effect and minimize the risk to toxicity.
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D002701:Chloramphenicol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate
D002701:Chloramphenicol; C026016:chloramphenicol succinate