Journal of Antimicrobial Chemotherapy, Vol 40, 91-98, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
GP Acharya, TM Davis, M Ho, S Harris, C Chataut, S Acharya, N Tuhladar, KE Kafle, B Pokhrel, F Nosten, DA Dance, A Smith, A Weber and NJ White
Chloramphenicol pharmacokinetics were studied in 29 Nepalese adults
diagnosed with uncomplicated enteric fever and randomized to receive
succinate ester 30 mg/kg i.v. or i.m. 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 i.v. chloramphenicol (mean +/- S.D.; 4.9 +/- 0.9 h and 1.9 +/- 0.8
L/kg; n = 7) were less than after i.m. 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 i.v. (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 i.v. and i.m. respectively). In 17 patients
examined during convalescence, MRT and Vdss 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 < 0.1) and were
higher in convalescence; no such associations were seen for iothalamate
Cl(p). These data indicate that i.v. chloramphenicol produces peak plasma
concentrations which are on average twice those after i.m. 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 i.v. dosing
is more likely to produce levels at which bone marrow toxicity occurs.
ORIGINAL ARTICLES
Factors affecting the pharmacokinetics of parenteral chloramphenicol in enteric fever
Tribhuvan University Teaching Hospital, Kathmandu, Nepal.
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