Estimation of Paracetamol in Urine to Assess the Diurnal Variation
Condition: Diurnal Variation of Paracetamol Excretion
Study type: Interventional

Summary: 
      Paracetamol is an antipyretic drug that is taken orally at different times of the day in same
      dose. It is excreted mainly through renal route which may show diurnal variation. In this
      study, urinary excretion of paracetamol of 41 healthy men of same age group will be measured
      by HPLC after oral administration of 500 mg paracetamol tablet at morning, midday and night.
      The measured values will be compared in order to adjust doses of oral paracetamol at
      different times of the day.
    

Detailed description: 
      Drug absorption, distribution, biotransformation and excretion are influenced by many
      different physiological functions of the body which may vary with time of the day. The time
      dependent changes in pharmacokinetics are due to circadian variation of human physiology and
      it is sometimes responsible for drug effects or adverse effects. Paracetamol is a widely used
      antipyretic and analgesic drug. It is usually well tolerated when used at the recommended
      dose. Paracetamol is a weak acidic drug that is rapidly absorbed and distributed after oral
      administration. It is metabolized extensively in liver and excrteted mainly through kidney as
      metabolites of paracetamol and some are as unchanged form. Paracetamol and its metabolites
      can be determined in biological fluids (urine, plasma, serum) by various mechanisms. High
      Performance Liquid Chromatography (HPLC) is a modern analytical chemistry technique by which
      paracetamol can be identified, separated and estimated from urine sample. This study is
      designed to investigate whether the excretion of paracetamol is changed or not if
      administered at same dose as oral tablet at three different times of the day. For this
      purpose after taking written informed consent 41 healthy men of aged 19- 23 will be provided
      500 mg oral paracetamol tablet at morning, midday and night in two weeks interval and
      estimation of urinary paracetamol will be done by HPLC after paracetamol ingestion. A pilot
      study has been done and result shows highest concentration of paracetamol in urine after its
      oral administration found at 4th hour. Urine sample will be collected before and 4 hour after
      paracetamol administration in chloroform containing urine container and will be preserved in
      - 20 ̊C until analysis. Paracetamol standard has been collected from the same pharmaceutical
      company of which the drug will be used for study. Mobile phase will be consist of
      acetonitrile and distilled water and flow rate will be 0.5 ml/min at 25 ̊C temperature and
      900 Psi pressure. The standard and sample will be analysed at a wavelength 254 nm. Total
      urinary paracetamol of that time will be estimated by multiplying total urinary volume in ml
      and concentration of paracetamol in one ml of urine. After measuring paracetamol at different
      times of the day, statistical analysis will be done to compare those values. If significant
      variation is found, adjustment of dose of oral paracetamol in different time of the day will
      be tried.
    

Intervention name(s): Paracetamol 500 mg tablet at morning; Paracetamol 500 mg tablet at midday; Paracetamol 500 mg tablet at night
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Single dose oral paracetamol will be administered at 8.00 am; Single dose oral paracetamol will be administered at 2.00 pm; Single dose oral paracetamol will be administered at 8.00 pm
Other intervention name(s): Tablet. Ace; Tablet. Ace; Tablet. Ace
Intervention MeSH terms: Acetaminophen
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Healthy Volunteers
Masking: None (Open Label)
Primary purpose: Diagnostic