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Sökning: id:"swepub:oai:DiVA.org:uu-224999" > Population pharmaco...

  • Zvada, Simbarashe P. (författare)

Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis : in silico evaluation of currently recommended doses

  • Artikel/kapitelEngelska2014

Förlag, utgivningsår, omfång ...

  • 2014-01-31
  • Oxford University Press (OUP),2014
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-224999
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-224999URI
  • https://doi.org/10.1093/jac/dkt524DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23 lower bioavailability compared with slow acetylators. Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Denti, Paolo (författare)
  • Donald, Peter R. (författare)
  • Schaaf, H. Simon (författare)
  • Thee, Stephanie (författare)
  • Seddon, James A. (författare)
  • Seifart, Heiner I. (författare)
  • Smith, Peter J. (författare)
  • McIlleron, Helen M. (författare)
  • Simonsson, Ulrika S. H.Uppsala universitet,Institutionen för farmaceutisk biovetenskap,farmakometri(Swepub:uu)usv12211 (författare)
  • Uppsala universitetInstitutionen för farmaceutisk biovetenskap (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Antimicrobial Chemotherapy: Oxford University Press (OUP)69:5, s. 1339-13490305-74531460-2091

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