Bioavailability of two licensed paediatric rifampicin suspensions: implications for quality control programmes

Area of Science:

• Pharmacology
• Pediatric Infectious Diseases
• Tuberculosis Treatment

Background:

• Rifampicin (RMP) is a cornerstone medication for tuberculosis (TB) treatment.
• Accurate dosing and consistent bioavailability are crucial for effective pediatric TB therapy.
• The World Health Organization recommends a revised RMP dose of 10-20 mg/kg for children.

Purpose of the Study:

• To assess the steady-state pharmacokinetics of rifampicin (RMP) in South African children.
• To evaluate the impact of different RMP oral suspension formulations on drug bioavailability.
• To inform optimal RMP dosing strategies for pediatric tuberculosis treatment.

Main Methods:

• Pharmacokinetic analysis of RMP plasma concentrations in 146 children with drug-susceptible TB.
• Administration of two different RMP single-drug oral suspension formulations.
• Comparison of 2-hour post-dose RMP concentrations between formulations and with adult data.

Main Results:

• Significant variability in RMP bioavailability was observed between the two tested oral suspension formulations.
• One formulation achieved RMP concentrations comparable to adult levels, while the other showed substantially lower bioavailability (median 25%).
• Median 2-hour RMP concentrations were 6.54 mg/l for the adequate formulation and 1.59 mg/l for the suboptimal one.

Conclusions:

• The formulation of rifampicin oral suspensions critically impacts drug bioavailability in children.
• Ensuring the quality and consistent bioavailability of RMP suspensions is essential for successful childhood TB treatment.
• Further research and quality control are needed for pediatric RMP formulations.