title: Pharmacokinetic interaction between zidovudine and trimethoprim/sulphamethoxazole in HIV-1 infected children.
abstract: OBJECTIVE
  To evaluate the effect of the antimicrobial agent trimethoprim/sulphamethoxazole (TMP/SMX) on the pharmacokinetic properties of the antiretroviral drug zidovudine (ZDV).
  
  
  METHODS
  This single dose, open label, crossover study involved the oral administration of ZDV (150 mg/m²) alone and in combination with oral TMP/SMX (2.5 mg/kg) on two separate occasions. Serial blood samples (0 to 8 h) were collected, and concentrations of ZDV and its glucuronide metabolite were quantified using a radioimmunoassay. ZDV pharmacokinetics were determined by noncompartmental analysis.
  
  
  METHODS
  Six HIV-1 infected children aged four months to five years were recruited from the HIV clinic at The Hospital for Sick Children, Toronto, Ontario. Only three patients completed both study phases and were included in the pharmacokinetic analysis.
  
  
  RESULTS
  With TMP/SMX therapy, no statistically significant changes were observed in ZDV pharmacokinetic parameters. However, there was a trend towards increased ZDV half-life and area under the concentration versus time curve, as well as decreased apparent oral clearance. Similarly, a trend towards an increased half-life of the ZDV-glucuronide metabolite was also observed.
  
  
  CONCLUSIONS
  The changes in ZDV pharmacokinetics in the presence of TMP/SMX did not reach statistical significance, most likely due to the limited number of patients involved. Despite the limited data, a possible interaction between ZDV and TMP/SMX in young HIV-1 infected children should be considered, and patients may require close clinical monitoring.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario.
authors.forename: S
authors.initials: S
authors.lastname: Dallas
authors.forename: S
authors.initials: S
authors.lastname: E Read
authors.forename: S
authors.initials: S
authors.lastname: King
authors.forename: G
authors.initials: G
authors.lastname: Koren
authors.forename: R
authors.initials: R
authors.lastname: Bendayan