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The development of a standardised screening protocol for the in vivo assessment of rifampicin bioavailability.
Int J Tuberc Lung Dis. 1999 Nov; 3(11 Suppl 3):S329-35; discussion S351-2.IJ

Abstract

SETTING

The prerequisite for in vivo bioavailability testing of rifampicin in fixed-dose combination (FDC) formulations is widely accepted. However, many smaller drug regulatory authorities and drug manufacturers have difficulty implementing costly and cumbersome testing procedures.

OBJECTIVE

To test whether a simplified blood sampling schedule can be used for the determination of drug bioequivalence in randomised, single dose, crossover studies of FDCs and appropriate reference formulations.

METHOD

The results of three bioavailability and bioequivalence studies of different rifampicin-containing FDCs were analysed. The relationship between the number of time points employed and precision of estimated relative bioavailability was explored. The relative bioavailabilities of the drug components in the test FDCs were calculated using maximal concentration and area under the curve estimates based on an extended blood sampling schedule of up to 15 time points over 48 hours, and a contracted sampling scheme with only six blood samples over 8 hours.

RESULTS

Estimates of relative bioavailability calculated using the contracted blood sampling protocol were closely similar to those derived using the extended sampling schedules.

CONCLUSION

Considerable cost and convenience benefits can be gained by using the contracted sampling schedule with only a minor reduction in the precision of the estimation of relative rifampicin bioavailability.

Authors+Show Affiliations

McIlleron H
Department of Pharmacology, University of Cape Town Medical School, Observatory, South Africa. hmciller@uctgshl.uct.ac.za
Gabriels G
No affiliation info available
Smith PJ
No affiliation info available
Fourie PB
No affiliation info available
Ellard GA
No affiliation info available

MeSH

AdolescentAdultAntibiotics, AntitubercularAntitubercular AgentsArea Under CurveBiological AvailabilityBlood Specimen CollectionChromatography, High Pressure LiquidCross-Over StudiesDrug CombinationsFemaleHumansMaleMiddle AgedQuality ControlRifampinTherapeutic EquivalencyTime Factors

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

10593713

Citation

McIlleron, H, et al. "The Development of a Standardised Screening Protocol for the in Vivo Assessment of Rifampicin Bioavailability." The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease, vol. 3, no. 11 Suppl 3, 1999, pp. S329-35; discussion S351-2.
McIlleron H, Gabriels G, Smith PJ, et al. The development of a standardised screening protocol for the in vivo assessment of rifampicin bioavailability. Int J Tuberc Lung Dis. 1999;3(11 Suppl 3):S329-35; discussion S351-2.
McIlleron, H., Gabriels, G., Smith, P. J., Fourie, P. B., & Ellard, G. A. (1999). The development of a standardised screening protocol for the in vivo assessment of rifampicin bioavailability. The International Journal of Tuberculosis and Lung Disease : the Official Journal of the International Union Against Tuberculosis and Lung Disease, 3(11 Suppl 3), S329-35; discussion S351-2.
McIlleron H, et al. The Development of a Standardised Screening Protocol for the in Vivo Assessment of Rifampicin Bioavailability. Int J Tuberc Lung Dis. 1999;3(11 Suppl 3):S329-35; discussion S351-2. PubMed PMID: 10593713.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The development of a standardised screening protocol for the in vivo assessment of rifampicin bioavailability. AU - McIlleron,H, AU - Gabriels,G, AU - Smith,P J, AU - Fourie,P B, AU - Ellard,G A, PY - 1999/12/11/pubmed PY - 1999/12/11/medline PY - 1999/12/11/entrez SP - S329-35; discussion S351-2 JF - The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease JO - Int J Tuberc Lung Dis VL - 3 IS - 11 Suppl 3 N2 - SETTING: The prerequisite for in vivo bioavailability testing of rifampicin in fixed-dose combination (FDC) formulations is widely accepted. However, many smaller drug regulatory authorities and drug manufacturers have difficulty implementing costly and cumbersome testing procedures. OBJECTIVE: To test whether a simplified blood sampling schedule can be used for the determination of drug bioequivalence in randomised, single dose, crossover studies of FDCs and appropriate reference formulations. METHOD: The results of three bioavailability and bioequivalence studies of different rifampicin-containing FDCs were analysed. The relationship between the number of time points employed and precision of estimated relative bioavailability was explored. The relative bioavailabilities of the drug components in the test FDCs were calculated using maximal concentration and area under the curve estimates based on an extended blood sampling schedule of up to 15 time points over 48 hours, and a contracted sampling scheme with only six blood samples over 8 hours. RESULTS: Estimates of relative bioavailability calculated using the contracted blood sampling protocol were closely similar to those derived using the extended sampling schedules. CONCLUSION: Considerable cost and convenience benefits can be gained by using the contracted sampling schedule with only a minor reduction in the precision of the estimation of relative rifampicin bioavailability. SN - 1027-3719 UR - https://www.unboundmedicine.com/medline/citation/10593713/The_development_of_a_standardised_screening_protocol_for_the_in_vivo_assessment_of_rifampicin_bioavailability_ DB - PRIME DP - Unbound Medicine ER -