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Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis

# metadata.dc.description.abstract[].value
Objectives: The objectives of this study were to explore inter-study heterogeneity in the pharmacokinetics (PK)
of orally administered rifampicin, to derive summary estimates of rifampicin PK parameters at standard dosages
and to compare these with summary estimates for higher dosages.
Methods: A systematic search was performed for studies of rifampicin PK published in the English language up
to May 2017. Data describing the Cmax and AUC were extracted. Meta-analysis provided summary estimates
for PK parameter estimates at standard rifampicin dosages. Heterogeneity was assessed by estimation of the
I
2 statistic and visual inspection of forest plots. Summary AUC estimates at standard and higher dosages were
compared graphically and contextualized using preclinical pharmacodynamic (PD) data.
Results: Substantial heterogeneity in PK parameters was evident and upheld in meta-regression. Treatment
duration had a significant impact on the summary estimates for rifampicin PK parameters, with Cmax 8.98 mg/L
(SEM 2.19) after a single dose and 5.79 mg/L (SEM 2.14) at steady-state dosing, and AUC 72.56 mgh/L
(SEM 2.60) and 38.73 mgh/L (SEM 4.33) after single and steady-state dosing, respectively. Rifampicin dosages of
at least 25 mg/kg are required to achieve plasma PK/PD targets defined in preclinical studies.
Conclusions: Vast inter-study heterogeneity exists in rifampicin PK parameter estimates. This is not explained by
the available modifying variables. The recommended dosage of rifampicin should be increased to improve efficacy. This study provides an important point of reference for understanding rifampicin PK at standard dosages
as efforts to explore higher dosing strategies continue in this field.

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Journal of Antimicrobial Chemotherapy, 2018, vol. 73, num. 9

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Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis