Metronidazole Pharmacokinetics (PK) in Premature Infants (PTN_METRO)
Yearly in the United States over 500,000 newborns are delivered prematurely. This population is at high risk of catastrophic bowel disease known as necrotizing enterocolitis. Infants with necrotizing enterocolitis are at high risk of death, and survivors are at increased risk of mental retardation. Metronidazole is an antibiotic that is often administered to infants with suspected or confirmed necrotizing enterocolitis. Unfortunately, the appropriate dose of metronidazole in premature infants has not been established and it is likely to be different from older children and adults.
The investigators will investigate the appropriate metronidazole dose in very premature infants by: 1) determining how premature infants eliminate metronidazole from the body and 2) determining the safest and most effective dose of metronidazole in premature infants.
The investigators hypothesis are: 1) The rate of removal of metronidazole will increase with infant maturity and 2) an appropriate metronidazole dosing regimen will result in necessary drug levels to treat bacteria involved in necrotizing enterocolitis.
|Serious Systemic Infections Necrotizing Enterocolitis||Drug: Metronidazole||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Safety and Pharmacokinetics of Multiple Dose Metronidazole in Premature Infants|
- Area Under the Curve at Steady State [ Time Frame: pre-dose: 30 min; post-dose:10 min, 3-4,6-8, 12-13, 24-25, 36-37, 48-49, 72-73 hours post dose ]Area under the curve at steady state (AUCss)
- Loading Dose Maximum Concentration [ Time Frame: 2-5 days of study drug administration ]Loading Dose Maximum concentration (Cmax)
- Loading Dose Minimum Concentration [ Time Frame: 2-5 days of study drug administration ]Loading Dose Minimum Concentration (mg/L)
- Multiple Dose Maximum Concentration [ Time Frame: 2-5 days of study drug administration ]Multiple Dose Maximum Concentration (mg/L)
- Multiple Dose Minimum Concentration [ Time Frame: 2-5 days of study drug administration ]Multiple Dose Minimum Concentration (mg/L)
- Clearance [ Time Frame: 2-5 days of study drug administration ]Clearance (L/h/kg)
- Volume of Distribution [ Time Frame: 2-5 days of study drug administration ]Volume of Distribution (L/kg)
|Study Start Date:||January 2011|
|Study Completion Date:||November 2011|
|Primary Completion Date:||November 2011 (Final data collection date for primary outcome measure)|
Intravenous metronidazole loading dose 15 mg/kg followed by 7.5 mg/kg every 12-24 hours
Metronidazole will be administered intravenously to premature infants as a 15 mg/kg loading dose followed by maintenance doses of 7.5 mg/kg every 12 hours for infants with >=14 postnatal days and every 24 hours for infants <14 postnatal days.
Other Name: Flagyl
Please refer to this study by its ClinicalTrials.gov identifier: NCT01222585
|United States, California|
|Orange, California, United States, 92868|
|United States, Kansas|
|Wesely Medical Center|
|Wichita, Kansas, United States, 67214|
|United States, North Carolina|
|Durham, North Carolina, United States, 27715|
|Principal Investigator:||Michael Cohen-wolkowiez, MD||Duke University|