Dosing regimens of oral ciprofloxacin for children with severe malnutrition: a population pharmacokinetic study with Monte Carlo simulation

Nahashon Thuo, Wanchana Ungphakorn, Japhet Karisa, Simon Muchohi, Alex Muturi, Gilbert Kokwaro, Alison H Thomson, Kathryn Maitland

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Abstract

Background Severe malnutrition is frequently complicated by sepsis, leading to high case fatality. Oral ciprofloxacin is a potential alternative to the standard parenteral ampicillin/gentamicin combination, but its pharmacokinetics in malnourished children is unknown. Methods Ciprofloxacin (10 mg/kg, 12 hourly) was administered either 2 h before or up to 2 h after feeds to Kenyan children hospitalized with severe malnutrition. Four plasma ciprofloxacin concentrations were measured over 24 h. Population analysis with NONMEM investigated factors affecting the oral clearance (CL) and the oral volume of distribution (V). Monte Carlo simulations investigated dosage regimens to achieve a target AUC(0-24)/MIC ratio of ≥125. Results Data comprised 202 ciprofloxacin concentration measurements from 52 children aged 8-102 months. Absorption was generally rapid but variable; C(max) ranged from 0.6 to 4.5 mg/L. Data were fitted by a one-compartment model with first-order absorption and lag. The parameters were CL (L/h) = 42.7 (L/h/70 kg) × [weight (kg)/70](0.75) × [1 + 0.0368 (Na(+) - 136)] × [1 - 0.283 (high risk)] and V (L) = 372 × (L/70 kg) × [1 + 0.0291 (Na(+) - 136)]. Estimates of AUC(0-24) ranged from 8 to 61 mg·h/L. The breakpoint for Gram-negative organisms was
Original languageEnglish
Pages (from-to)2336-2345
Number of pages10
JournalJournal of Antimicrobial Chemotherapy
Volume66
Issue number10
Early online date10 Aug 2011
DOIs
Publication statusPublished - 2011

Keywords

  • quinolone
  • drug absorption
  • marasmus
  • kwashiorkor
  • gram-negative

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