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


Authors: Thuo, Nahashon; Ungphakorn, Wanchana; Karisa, Japhet; Muchohi, Simon; Muturi, Alex; Kokwaro, Gilbert; Thomson, Alison H.; Maitland, Kathryn
Article Title: Dosing regimens of oral ciprofloxacin for children with severe malnutrition: a population pharmacokinetic study with Monte Carlo simulation.
Keywords: CIPROFLOXACIN; PHARMACOKINETICS; MALNUTRITION; MONTE Carlo method; QUINOLONE antibacterial agents; GRAM-negative bacteria; drug absorption; Gram-negative; kwashiorkor; marasmus; quinolone
Journal Title: Journal of Antimicrobial Chemotherapy (JAC)
Volume: 66
Issue: 10
ISSN: 03057453
Publisher: Unknown  
Date Published: 2011-10
Start Page: 2336
End Page: 2345
DOI/URL:
Notes: --- - Article - 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 AUC0–24/MIC ratio of ?125. Results Data comprised 202 ciprofloxacin concentration measurements from 52 children aged 8–102 months. Absorption was generally rapid but variable; Cmax 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 AUC0–24 ranged from 8 to 61 mg·h/L. The breakpoint for Gram-negative organisms was <0.06 mg/L with doses of 20 mg/kg/day and <0.125 mg/L with doses of 30 or 45 mg/kg/day. The cumulative fraction of response with 30 mg/kg/day was ?80% for Escherichia coli, Klebsiella pneumoniae and Salmonella species, but <60% for Pseudomonas aeruginosa. Conclusions An oral ciprofloxacin dose of 10 mg/kg three times daily (30 mg/kg/day) may be a suitable alternative antibiotic for the management of sepsis in severely malnourished children. Absorption was unaffected by the simultaneous administration of feeds. [ABSTRACT FROM PUBLISHER] - Copyright of Journal of Antimicrobial Chemotherapy (JAC) is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) - ! 'Accession Number: 65574919; Thuo, Nahashon 1 Ungphakorn, Wanchana 2 Karisa, Japhet 1 Muchohi, Simon 1 Muturi, Alex 1 Kokwaro, Gilbert 3,4 Thomson, Alison H. 2,5 Maitland, Kathryn 1,6; Affiliation: 1: KEMRI-Wellcome Trust Research Programme , Centre for Geographic Medicine Research (Coast) , PO Box 230, 80108 Kilifi , Kenya 2: Strathclyde Institute of Pharmacy and Biomedical Sciences , University of Strathclyde , 161 Cathedral Street, Glasgow G4 0RE , UK 3: Department of Pharmaceutics and Pharmacy Practice, School of Pharmacy , University of Nairobi , Nairobi , Kenya 4: The Consortium for National Health Research (CNHR ) , PO Box 29832, Nairobi 00202 , Kenya 5: Pharmacy Department, Pharmacy and Prescribing Support Unit , Western Infirmary, NHS Greater Glasgow and Clyde , Glasgow G11 6NT , UK 6: Wellcome Trust Centre for Clinical Tropical Medicine, Faculty of Medicine , Imperial College , Norfolk Place, London W2 1PG , UK; Source Info: Oct2011, Vol. 66 Issue 10, p2336; Subject Term: MALNUTRITION; Subject Term: MONTE Carlo method; Subject Term: CIPROFLOXACIN; Subject Term: PHARMACOKINETICS; Subject Term: QUINOLONE antibacterial agents; Subject Term: GRAM-negative bacteria; Author-Supplied Keyword: drug absorption; Author-Supplied Keyword: Gram-negative; Author-Supplied Keyword: kwashiorkor; Author-Supplied Keyword: marasmus; Author-Supplied Keyword: quinolone; Number of Pages: 10p; Document Type: Article'
SU Authors
  1. Prof. Gilbert Kokwaro
    26 Kokwaro