Estimation of Paracetamol in Urine to Assess the Diurnal Variation

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.

Study Overview

• Status: Completed
• Conditions: Diurnal Variation of Paracetamol Excretion
• Intervention / Treatment: Drug: Paracetamol 500 mg tablet at morning; Drug: Paracetamol 500 mg tablet at midday; Drug: Paracetamol 500 mg tablet at night

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Bangladesh
  • Comilla, Bangladesh, 3500
    • Eastern Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 23 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• The healthy male student volunteers of Eastern Medical College having age range between 19 and 23 years

Exclusion Criteria:

• Age <19 years , >23 years
• Volunteers on analgesic or antipyretic medication
• Volunteers with history of hypersensitivity to paracetamol
• Volunteers taking any enzyme inducing or enzyme inhibiting drug
• Volunteers with impaired renal or hepatic function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Paracetamol 500 mg tablet at Morning; Urinary paracetamol of 41 healthy volunteers will be measured after oral administration at morning	Drug: Paracetamol 500 mg tablet at morning; Single dose oral paracetamol will be administered at 8.00 am; Other Names: Tablet. Ace
Other: Paracetamol 500 mg tablet at Midday; Urinary paracetamol of 41 healthy volunteers will be measured after oral administration at midday	Drug: Paracetamol 500 mg tablet at midday; Single dose oral paracetamol will be administered at 2.00 pm; Other Names: Tablet. Ace
Other: Paracetamol 500 mg tablet at Night; Urinary paracetamol of 41 healthy volunteers will be measured after oral administration at night	Drug: Paracetamol 500 mg tablet at night; Single dose oral paracetamol will be administered at 8.00 pm; Other Names: Tablet. Ace

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the amount of urinary paracetamol in different times	Changes in the amount of urinary paracetamol in different times (morning, midday and night) 4 hours after oral administration of 500 mg of paracetamol	[Morning: 0 hour (baseline), 4 hour (end); Mid-day: 0 hour (baseline), 4 hour (end); Night: 0 hour (baseline), 4 hour (end)] [Safety Issue: No]

Collaborators and Investigators

• Sponsor: Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2016
• Primary Completion (Actual): January 30, 2018
• Study Completion (Actual): January 30, 2018

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 20, 2017
• First Posted (Actual): April 21, 2017

Study Record Updates

• Last Update Posted (Actual): July 13, 2018
• Last Update Submitted That Met QC Criteria: July 12, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: BSMMU-013-CT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No