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Statistical evaluation of physiological variability of rifampicin in fixed dose combinations.
Int J Pharm. 2006 Apr 26; 313(1-2):5-13.IJ

Abstract

Tuberculosis is one of the microbial diseases having a long history of its occurrence and yet to be eradicated from the world. Due to the development of bacterial resistance, treatment has changed from monotherapy to combotherapy to fixed dose combinations (FDCs). Rifampicin has been found one of the most important anti-tubercular drugs, however variable bioavailability of rifampicin in some FDCs as well as separate formulations has been reported in the literature, and led to the development of WHO model protocol for evaluation of FDCs for bioequivalence trials. In present investigation, role of physiological variability in rifampicin bioequivalence was studied. Influence of subject's body weight, inter/intra-individual variability of elimination rate and impact of outliers on the decision of bioequivalence were investigated. Normalization of pharmacokinetic measures for bioequivalence (AUC and C(max)) were carried out as per body weights and elimination rate constants of subjects, then different statistical tests like two-way ANOVA, hauschke analysis, normal and log-transformed confidence interval were applied to check for the change in bioequivalence decision. It was found that normalization as per body weights did not play a significant role in the outcome of bioequivalence endpoint. Similarly, elimination rate variability and outliers have been found insignificant regarding final outcome of bioequivalence study. Hence, it has been concluded that physiological variability did not play a significant role in bioequivalence of rifampicin in FDCs.

Authors+Show Affiliations

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Mohali, Punjab, India. panchagnula@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16517107

Citation

Panchagnula, Ramesh, et al. "Statistical Evaluation of Physiological Variability of Rifampicin in Fixed Dose Combinations." International Journal of Pharmaceutics, vol. 313, no. 1-2, 2006, pp. 5-13.
Panchagnula R, Parmar J, Kaur K, et al. Statistical evaluation of physiological variability of rifampicin in fixed dose combinations. Int J Pharm. 2006;313(1-2):5-13.
Panchagnula, R., Parmar, J., Kaur, K., Singh, I., Bade, S. R., & Ashokraj, Y. (2006). Statistical evaluation of physiological variability of rifampicin in fixed dose combinations. International Journal of Pharmaceutics, 313(1-2), 5-13.
Panchagnula R, et al. Statistical Evaluation of Physiological Variability of Rifampicin in Fixed Dose Combinations. Int J Pharm. 2006 Apr 26;313(1-2):5-13. PubMed PMID: 16517107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Statistical evaluation of physiological variability of rifampicin in fixed dose combinations. AU - Panchagnula,Ramesh, AU - Parmar,Jitendra, AU - Kaur,Kanwaljit, AU - Singh,Inderjit, AU - Bade,Shantaram Ramdos, AU - Ashokraj,Yasvanth, Y1 - 2006/03/06/ PY - 2005/11/15/received PY - 2005/12/29/accepted PY - 2006/3/7/pubmed PY - 2006/10/20/medline PY - 2006/3/7/entrez SP - 5 EP - 13 JF - International journal of pharmaceutics JO - Int J Pharm VL - 313 IS - 1-2 N2 - Tuberculosis is one of the microbial diseases having a long history of its occurrence and yet to be eradicated from the world. Due to the development of bacterial resistance, treatment has changed from monotherapy to combotherapy to fixed dose combinations (FDCs). Rifampicin has been found one of the most important anti-tubercular drugs, however variable bioavailability of rifampicin in some FDCs as well as separate formulations has been reported in the literature, and led to the development of WHO model protocol for evaluation of FDCs for bioequivalence trials. In present investigation, role of physiological variability in rifampicin bioequivalence was studied. Influence of subject's body weight, inter/intra-individual variability of elimination rate and impact of outliers on the decision of bioequivalence were investigated. Normalization of pharmacokinetic measures for bioequivalence (AUC and C(max)) were carried out as per body weights and elimination rate constants of subjects, then different statistical tests like two-way ANOVA, hauschke analysis, normal and log-transformed confidence interval were applied to check for the change in bioequivalence decision. It was found that normalization as per body weights did not play a significant role in the outcome of bioequivalence endpoint. Similarly, elimination rate variability and outliers have been found insignificant regarding final outcome of bioequivalence study. Hence, it has been concluded that physiological variability did not play a significant role in bioequivalence of rifampicin in FDCs. SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/16517107/Statistical_evaluation_of_physiological_variability_of_rifampicin_in_fixed_dose_combinations_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(06)00006-8 DB - PRIME DP - Unbound Medicine ER -