Rifampin Pharmacokinetics and Safety in Preterm and Term Infants

Antimicrob Agents Chemother. 2019 May 24;63(6):e00284-19. doi: 10.1128/AAC.00284-19. Print 2019 Jun.

Abstract

Rifampin is active against methicillin-resistant staphylococcal species and tuberculosis (TB). We performed a multicenter, prospective pharmacokinetic (PK) and safety study of intravenous rifampin in infants of <121 days postnatal age (PNA). We enrolled 27 infants; the median (range) gestational age was 26 weeks (23 to 41 weeks), and the median PNA was 10 days (0 to 84 days). We collected 102 plasma PK samples from 22 of the infants and analyzed safety data from all 27 infants. We analyzed the data using a population PK approach. Rifampin PK was best characterized by a one-compartment model; drug clearance increased with increasing size (body weight) and maturation (PNA). There were no adverse events related to rifampin. Simulated weight and PNA-based intravenous dosing regimens administered once daily (<14 days PNA, 8 mg/kg; ≥14 days PNA, 15 mg/kg) in infants resulted in comparable exposures to adults receiving therapeutic doses of rifampin against staphylococcal infections and TB. (This study has been registered at ClinicalTrials.gov under identifier NCT01728363.).

Keywords: MRSA; infants; pediatrics; population pharmacokinetics; rifampin; safety.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Female
  • Gestational Age
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature / metabolism*
  • Male
  • Prospective Studies
  • Rifampin / adverse effects*
  • Rifampin / pharmacokinetics*
  • Rifampin / therapeutic use
  • Staphylococcal Infections / drug therapy
  • Staphylococcal Infections / metabolism
  • Tuberculosis / drug therapy
  • Tuberculosis / metabolism

Substances

  • Rifampin

Associated data

  • ClinicalTrials.gov/NCT01728363