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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. ISSN 1460-2091

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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

Item type: Article
ID code: 34691
Keywords: quinolone, drug absorption, marasmus, kwashiorkor, gram-negative, Pharmacy and materia medica, Infectious Diseases, Pharmacology, Pharmacology (medical)
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 19 Oct 2011 15:19
    Last modified: 13 Jun 2014 05:08
    URI: http://strathprints.strath.ac.uk/id/eprint/34691

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