Factors affecting the pharmacokinetics of parenteral chloramphenicol in enteric fever

G. Acharya, Timothy Davis, M. Ho, S. Harris, C. Chataut, S. Acharya, N. Tuhlader, K. Kafle, F. Nosten, D. Dance, A. Smith, N. White

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    11 Citations (Scopus)

    Abstract

    Chloramphenicol pharmacokinetics were studied in 29 Nepalese adults diagnosed with uncomplicated enteric fever and randomized to receive succinate ester 30 mg/kg iv or im. Serial plasma concentrations of chloramphenicol, and iothalamate (to estimate glomerular filtration rate), antipyrine (hepatocellular function) and Indocyanine Green (liver blood flow) were measured by HPLC and kinetic parameters estimated by non-compartmental analysis. In culture-positive patients (n = 16), mean residence times (MRTs) and steady-state volumes of distribution (V(d)ss) for iv chloramphenicol (mean +/- S.D.; 4.9 +/- 0.9 h and 1.9 +/- 0.8 L/kg; n = 7) were less than after im chloramphenicol (12.3 +/- 7.3 h and 3.7 +/- 2.5 L/kg; n = 9; P <0.05), with a higher peak plasma concentration after iv (16.2 +/- 9.1 versus 7.8 +/- 3.6 mg/L; P <0.05); plasma clearance (Cl-p) was similar in the two groups (368 +/- 172 and 310 +/- 224 mL/kg/min after iv and im respectively). In 17 patients examined during convalescence, MRT and V(d)ss were less than in acute illness regardless of route chloramphenicol administration. There were similar changes in chloramphenicol kinetic parameters in culture-negative patients. Antipyrine Cl-p and liver blood flow correlated weakly with chloramphenicol Cl-p in culture-positive patients (P less than or equal to 0.1) and were higher in convalescence; no such associations were seen for iothalamate Cl-p. These data indicate that iv chloramphenicol produces peak plasma concentrations which are on average twice those after im injection of the same dose, due principally to a smaller V(d)ss. Cl-p is uninfluenced by route of administration and is determined more by hepatic metabolism than renal excretion. Intramuscular treatment may result in sub-therapeutic chloramphenicol concentrations initially, but continued regular iv dosing is more likely to produce levels at which bone marrow toxicity occurs.
    Original languageEnglish
    Pages (from-to)91-98
    JournalJournal of Antimicrobial Chemotherapy
    Volume40
    DOIs
    Publication statusPublished - 1997

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