Codeine Phosphate Hemihydrate

This article discusses a clinical trial investigating the bioequivalence of a new single-tablet formulation of paracetamol and codeine phosphate hemihydrate compared to a standard two-tablet formulation. The study aims to evaluate the rate and extent of absorption of these medications in healthy volunteers under fasting conditions. Understanding the results of this trial could lead to more convenient dosing options for patients requiring pain relief.

What is Codeine Phosphate Hemihydrate?
Uses and Conditions Treated
New Formulation and Bioequivalence Study
Administration and Dosage
Pharmacokinetics: How the Body Processes Codeine
Safety and Side Effects

What is Codeine Phosphate Hemihydrate?

Codeine Phosphate Hemihydrate is a medication that belongs to a class of drugs known as opioid analgesics. It is commonly used in combination with other pain relievers, such as paracetamol (also known as acetaminophen), to manage moderate pain^[1]. The term “hemihydrate” refers to the chemical structure of the compound, which includes half a molecule of water for each molecule of codeine phosphate.

Uses and Conditions Treated

While the clinical trial data provided doesn’t explicitly state the conditions treated by Codeine Phosphate Hemihydrate, it’s generally used for:

Pain management: Codeine is often combined with paracetamol to treat moderate pain that isn’t relieved by other painkillers alone.
Cough suppression: Although not mentioned in the trial data, codeine is also known for its cough-suppressing properties.

It’s important to note that in the clinical trial, the medication was tested on healthy volunteers, which is common practice in bioequivalence studies to assess how the drug behaves in the body without the influence of any medical conditions^[1].

New Formulation and Bioequivalence Study

The clinical trial data describes a study comparing a new formulation of codeine and paracetamol to an existing one:

New formulation: One tablet containing 1000 mg of paracetamol and 30 mg of codeine phosphate hemihydrate.
Existing formulation (reference product): Two tablets of Co-efferalgan®, each containing 500 mg of paracetamol and 30 mg of codeine phosphate hemihydrate.

The purpose of this study was to determine if the new single-tablet formulation is bioequivalent to the existing two-tablet formulation. Bioequivalence means that the two formulations have the same effect and behave similarly in the body^[1].

Administration and Dosage

In the clinical trial:

The new formulation was administered as a single tablet of paracetamol 1000 mg/codeine 30 mg.
The reference formulation was given as two tablets of paracetamol 500 mg/codeine 30 mg.

Both formulations were given as a single dose under fasting conditions (meaning participants hadn’t eaten before taking the medication). It’s important to note that this dosing was specific to the clinical trial and may not reflect typical patient dosing. Always follow your healthcare provider’s instructions for taking any medication^[1].

Pharmacokinetics: How the Body Processes Codeine

The study measured several aspects of how the body processes codeine and paracetamol, known as pharmacokinetics. These include:

Cmax: The maximum concentration of the drug in the blood.
AUC (Area Under the Curve): A measure of the total exposure to the drug over time.
Tmax: The time it takes to reach the maximum concentration.
Half-life: The time it takes for the concentration of the drug in the body to be reduced by half.

These measurements were taken at various time points from 5 minutes to 36 hours after taking the medication, allowing researchers to understand how quickly the drugs are absorbed, how long they stay in the body, and how they are eliminated^[1].

Safety and Side Effects

While the primary focus of the study was on bioequivalence, safety was also monitored. The researchers looked at:

Treatment-Emergent Adverse Events (TEAEs): Any new side effects or worsening of existing conditions that occur after starting the treatment.
Vital signs: Including blood pressure (BP) and heart rate (HR).
Physical examinations
Laboratory parameters
Body weight
ECG (Electrocardiogram): A test that checks for problems with the electrical activity of your heart.

These safety measures were monitored throughout the study period. It’s important to remember that all medications can have side effects, and you should always discuss potential risks and benefits with your healthcare provider^[1].

Aspect	Details
Study Type	Bioequivalence study
Medications Compared	One tablet of Paracetamol 1000 mg/Codeine 30 mg vs. Two tablets of Paracetamol 500 mg/Codeine 30 mg
Participants	Healthy male and female volunteers
Study Design	Two-period, single-dose administration with washout period
Primary Outcomes	Cmax and AUC(0-t) for paracetamol and codeine
Secondary Outcomes	AUC(0-∞), Tmax, Terminal half-life, Apparent First Order Terminal Rate Constant, Time Until First Nonzero Concentration, Safety assessments
Safety Monitoring	Adverse events, vital signs, physical examinations, laboratory parameters, body weight, ECG

Aspect

Details

Study Type

Bioequivalence study

Medications Compared

One tablet of Paracetamol 1000 mg/Codeine 30 mg vs. Two tablets of Paracetamol 500 mg/Codeine 30 mg

Participants

Healthy male and female volunteers

Study Design

Two-period, single-dose administration with washout period

Primary Outcomes

Cmax and AUC(0-t) for paracetamol and codeine

Secondary Outcomes

AUC(0-∞), Tmax, Terminal half-life, Apparent First Order Terminal Rate Constant, Time Until First Nonzero Concentration, Safety assessments

Safety Monitoring

Adverse events, vital signs, physical examinations, laboratory parameters, body weight, ECG

Ongoing Clinical Trials on Codeine Phosphate Hemihydrate

Glossary

Bioequivalence: A comparison of the biological equivalence of two products with the same active ingredient, ensuring they have the same effect in the body.
Paracetamol: Also known as acetaminophen, it is a pain-relieving and fever-reducing medication.
Codeine Phosphate Hemihydrate: A form of codeine, an opioid medication used for pain relief and cough suppression.
Cmax: The maximum concentration of a drug in the blood after administration.
AUC (Area Under the Curve): A measure of the total exposure to a drug over time, used to assess how much of the drug is absorbed by the body.
Fasting conditions: A state where participants have not eaten for a specific period before taking the medication.
Washout period: The time between different treatments in a study, allowing the body to clear the previous medication.
Plasma concentration: The amount of a drug present in the blood plasma at a given time.
Terminal half-life: The time it takes for the concentration of a drug in the body to decrease by half after the distribution phase.
Treatment-Emergent Adverse Event (TEAE): Any unfavorable medical occurrence that appears or worsens after starting a medical treatment.

References

https://clinicaltrials.gov/study/NCT02902666

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