Abstract
Current guidelines for dosing of anti-TB drugs in children advocate higher doses for rifampicin and isoniazid despite limited availability of paediatric data on the pharmacokinetics of these drugs, especially from Africa, where the burden of childhood disease remains high. Thirty children aged 6 months to 15 years underwent intensive pharmacokinetic sampling for first-line anti-TB drugs at Queen Elizabeth Central Hospital, Blantyre, Malawi. Rifampicin, isoniazid, pyrazinamide and ethambutol were dosed at 10, 5, 25 and 20 mg/kg, respectively. Plasma drug concentrations were determined using sensitive, validated bioanalytical methods and summary pharmacokinetic parameters were estimated using non-compartmental analysis. The median (IQR) Cmax was 2.90 (2.08-3.43), 3.37 (2.55-4.59), 34.60 (32.30-40.90) and 1.20 (0.85-1.68) mg/L while the median (IQR) AUC0-∞ was 16.92 (11.10-22.74), 11.48 (7.35-18.93), 333.50 (279.50-487.2) and 8.65 (5.96-11.47) mg·h/L for rifampicin, isoniazid, pyrazinamide and ethambutol, respectively. For all drugs, pharmacokinetic parameters relating to drug absorption and exposure were lower than those published for adults, though similar to existing paediatric data from sub-Saharan Africa. Weight and/or dose p...Continue Reading
References
Sep 2, 1972·British Medical Journal·J C Waterlow
Sep 1, 1995·Annals of Tropical Paediatrics·H I SeifartP P Jaarsveld
May 24, 2005·Archives of Disease in Childhood·H S SchaafP R Donald
Jan 27, 2006·Antimicrobial Agents and Chemotherapy·S M GrahamE M Molyneux
Mar 30, 2006·Antimicrobial Agents and Chemotherapy·Helen McIlleronPete Smith
Feb 29, 2008·BMC Genetics·Audrey SabbaghEstella S Poloni
Apr 24, 2009·BMC Medicine·Hendrik Simon SchaafPeter Roderick Donald
Apr 28, 2009·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Helen McIlleronPeter R Donald
Jan 23, 2010·Biologicals : Journal of the International Association of Biological Standardization·UNKNOWN WHO
Mar 19, 2011·The Pediatric Infectious Disease Journal·Helen McIlleronPeter Roderick Donald
Mar 25, 2011·Tuberculosis·P R DonaldA H Diacon
Jul 29, 2011·Tuberculosis·P R DonaldA H Diacon
Oct 5, 2011·Antimicrobial Agents and Chemotherapy·S TheeH S Schaaf
Oct 15, 2011·Pharmacogenomics·Holly M MortensenSarah A Tishkoff
Feb 18, 2012·The European Respiratory Journal·Andreas SandgrenStephen M Graham
May 17, 2013·The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease·P R DonaldA C Hesseling
Jul 9, 2013·Archives of Disease in Childhood·Brian J Anderson, Nick H G Holford
Citations
Nov 3, 2016·Expert Review of Clinical Pharmacology·Bella Devaleenal DanielSoumya Swaminathan
Nov 28, 2015·British Journal of Clinical Pharmacology·A SchipaniG Davies
Jun 20, 2018·Antimicrobial Agents and Chemotherapy·Yasuhiro HoritaCharles A Peloquin
May 4, 2017·Antimicrobial Agents and Chemotherapy·Derek J SloanGeraint R Davies
Jan 27, 2016·Antimicrobial Agents and Chemotherapy·A BekkerA C Hesseling
Aug 8, 2015·Antimicrobial Agents and Chemotherapy·J J van OosterhoutS Ward
Nov 27, 2018·Expert Review of Clinical Pharmacology·Fiona V CresswellReinout Van Crevel
Jun 17, 2016·European Journal of Clinical Pharmacology·Roger K VerbeeckTim W Rennie
Mar 28, 2019·Indian Journal of Pediatrics·Aparna MukherjeeS K Kabra