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Pharmacokinetics of trimethoprim given in single daily doses for three days
Abstract:
Trimethoprim in a single daily dose of 300 mg was administered at night to 8 healthy volunteers for 3 days. Serum concentrations of trimethoprim were measured after 12, 36, 60 and 84 h. The average trimethoprim concentrations were 3.0, 4.0, 4.7 and 0.96 micrograms/ml, respectively. The urinary concentrations were in excess of the minimum inhibitory concentration for most urinary pathogens for up to 5 days after the start of oral medication. The individual variation in bioavailability and urinary excretion was reflected in the varying amount of unchanged trimethoprim excreted in the urine, between 66 and 95%.
Insights
Single daily nighttime doses of trimethoprim (300 mg) maintained effective urinary concentrations for up to five days in healthy volunteers. Bioavailability and excretion varied significantly among individuals.
Area of Science:
- Pharmacokinetics
- Clinical Pharmacology
- Antimicrobial Agents
Background:
- Trimethoprim is a widely used antibiotic for urinary tract infections.
- Understanding its pharmacokinetic profile is crucial for optimizing dosing regimens.
- Previous studies have established its efficacy, but detailed concentration-time data after specific dosing schedules are valuable.
Purpose of the Study:
- To evaluate the serum and urinary concentrations of trimethoprim following a single daily nighttime oral dose.
- To determine the duration for which urinary trimethoprim concentrations remain above the minimum inhibitory concentration (MIC) for common urinary pathogens.
- To assess the inter-individual variability in trimethoprim bioavailability and urinary excretion.
Main Methods:
- Eight healthy volunteers received 300 mg of trimethoprim orally once daily at night for three consecutive days.
- Serum trimethoprim concentrations were measured at 12, 36, 60, and 84 hours post-administration.
- Urinary concentrations were assessed to determine the duration above MIC.
- Urinary excretion of unchanged trimethoprim was quantified to assess bioavailability and variability.
Main Results:
- Average serum trimethoprim concentrations peaked around 4.7 micrograms/ml at 60 hours.
- Urinary concentrations exceeded the MIC for most urinary pathogens for up to 5 days after initiating treatment.
- The percentage of unchanged trimethoprim excreted in urine varied widely, ranging from 66% to 95% among individuals.
Conclusions:
- A single daily nighttime 300 mg dose of trimethoprim provides sustained therapeutic urinary concentrations.
- The observed variability in bioavailability and excretion highlights the importance of considering individual patient factors.
- This dosing regimen appears effective for maintaining antimicrobial activity against urinary pathogens for an extended period.