A Randomized, Single-blind, Parallel Group and Multiple - Dose Design Study

Acetaminophen (AAP) is the most popular used analgesic/ antipyretic drug with serious hepatotoxic adverse effects; suicidal or unintentional overdose of AAP-induced hepatotoxicity. Cytochrome P450 2E1 (CYP2E1) is thought contribute to the responsible reactive metabolite N-acetyl-p-benzoquinone (NAPQI) of AAP overdose-induced hepatotoxicity. Pharmaceutical excipients are inactive ingredients that are added to a pharmaceutical compound. The objective of this study was to investigate the possible response of Panadol® (AAP alone) and SafeTynadol® (AAP with various selected excipients combination) formulations, while observing the AAP toxic metabolites (AAP-Cys) circumstances change in healthy volunteers. According to the current safety data, could be potentially develop hepatotoxicity-free AAP new formulation drug.

Inclusion criteria

• Normal healthy adult subjects between 20-50 years of age.
• Body weight within 80-120% of ideal body weight. Male: Ideal body weight = (height - 80) * 0.7 Female: Ideal body weight = (height - 70) * 0.6
• Acceptable medical history and physical examination including:

• normal ECG results within six months prior to Period I (or Period III or Period V) dosing.
• no particular clinical significance in general disease history within two months prior to Period I (or Period III or Period V) dosing.
• Acceptable clinical laboratory determinations without significant deviation from normal values within two months prior to Period I (or Period III or Period V) dosing, which includes AST (SGOT), ALT (SGPT), r-GT, alkaline phosphatase, total bilirubin, albumin, glucose, BUN, uric acid, creatinine, total cholesterol, triglyceride (TG) and oral galactose single point (OGSP).
• Acceptable hematology within two months prior to the study, which includes hemoglobin, hematocrit, red blood cells, MCV, MCH, MCHC, white blood cells, differential white blood cells and platelets.
• Acceptable urinalysis within two months prior to the study, which includes pH, blood, glucose and protein.
• Signed the written informed consent to participate in this study.

Exclusion criteria

• History or presence of alcohol abuse, defined as consumption of more than 210 mL of alcohol per week (the equivalent of 14 glasses of 120-mL wine or 14 cans of 350-mL beer), or other substance abuse within the prior two years.
• A clinically significant disorder involving the allergy, cardiovascular, respiratory, renal, gastrointestinal/hepatic, immunologic, hematologic, endocrine or neurologic system(s) or psychiatric disease (as determined by the clinical investigator).
• History of allergic response(s) to acetaminophen, mannitol, sucralose or related drugs.
• History of clinically significant allergies including drug allergies or allergic bronchial asthma.
• Evidence of chronic or acute infectious diseases.
• Any clinically significant illness or surgery during the one month prior to Period I (or Period III or Period V) dosing (as determined by the clinical investigator).
• Taking any drug known to induce or inhibit hepatic drug metabolism within one month prior to the beginning of the study.
• Receiving any investigational drug within one month prior to Period I (or Period III or Period V) dosing.
• Taking any prescription medication or any nonprescription medication within two weeks prior to Period I (or Period III or Period V) doing.
• Donating greater than 150 ml of blood within two months prior to Period I (or Period III or Period V) dosing or donating plasma (e.g. plasmapheresis) within two weeks prior to Period I (or Period III or Period V) dosing.
• Consumption of caffeine, xanthine-containing products (i.e. coffee, tea, caffeine-containing sodas, colas and chocolate, etc.) and/or alcohol within 48 hours prior to days on which dosing is scheduled and during the periods when blood samples are being collected.
• Any other medical reason as determined by the clinical investigator.
• Subject is pregnant or breastfeeding.
• Women of childbearing potential disagree to use an acceptable method of contraception (e.g., hormonal contraceptives, IUD, barrier device or abstinence) throughout the study.