The WHO simplified study protocol in practice: investigation of combined formulations supplied by the WHO

Int J Tuberc Lung Dis. 1999 Nov;3(11 Suppl 3):S336-42; discussion S351-2.

Abstract

Setting: The benefits of fixed-dose combination (FDC) formulations of rifampicin, isoniazid and pyrazinamide over individual formulations are well recognised.

Objectives: To evaluate the comparative bioavailability of antituberculosis drugs in FDC formulations and the same doses in separate formulations of antituberculosis drugs, using a simplified protocol developed by the World Health Organization (WHO).

Methods: Twenty healthy volunteers were included in the study and evaluated for bioequivalence of rifampicin in a cross-over experimental design. After administration of drugs the plasma concentration of rifampicin and desacetyl-rifampicin was measured repeatedly up to 8 hours in both plasma and urine. Various pharmacokinetic parameters of rifampicin, such as Cmax, Tmax, elimination rate constant, area under the curve (AUC) up to 8 hours and absorption efficiency were calculated.

Results: No significant differences were observed between the FDCs and separate formulations when Cmax, Tmax, AUC and absorption efficiencies were compared by parametric test and Hauschke's analysis.

Conclusion: The WHO simplified protocol is suitable for evaluating bioequivalence of antituberculosis drugs.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Antibiotics, Antitubercular / administration & dosage
  • Antibiotics, Antitubercular / blood
  • Antibiotics, Antitubercular / pharmacokinetics
  • Antibiotics, Antitubercular / urine
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / blood
  • Antitubercular Agents / pharmacokinetics*
  • Antitubercular Agents / urine
  • Area Under Curve
  • Biological Availability
  • Clinical Protocols
  • Creatinine / urine
  • Cross-Over Studies
  • Drug Combinations
  • Humans
  • Male
  • Middle Aged
  • Rifampin / administration & dosage*
  • Rifampin / analogs & derivatives
  • Rifampin / blood
  • Rifampin / pharmacokinetics*
  • Rifampin / urine
  • Therapeutic Equivalency
  • World Health Organization*

Substances

  • Antibiotics, Antitubercular
  • Antitubercular Agents
  • Drug Combinations
  • Creatinine
  • 25-deacetylrifampicin
  • Rifampin