Picture of a sphere with binary code

Making Strathclyde research discoverable to the world...

The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs. It exposes Strathclyde's world leading Open Access research to many of the world's leading resource discovery tools, and from there onto the screens of researchers around the world.

Explore Strathclyde Open Access research content

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

Thuo, Nahashon and Ungphakorn, Wanchana and Karisa, Japhet and Muchohi, Simon and Muturi, Alex and Kokwaro, Gilbert and Thomson, Alison H and Maitland, Kathryn (2011) Dosing regimens of oral ciprofloxacin for children with severe malnutrition : a population pharmacokinetic study with Monte Carlo simulation. Journal of Antimicrobial Chemotherapy, 66 (10). pp. 2336-2345.

Full text not available in this repository. (Request a copy from the Strathclyde author)

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