Compounds > pyridoxal phosphate
Page last updated: 2024-10-20

pyridoxal phosphate and Acute Liver Injury, Drug-Induced

pyridoxal phosphate has been researched along with Acute Liver Injury, Drug-Induced in 11 studies

Pyridoxal Phosphate: This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE).
pyridoxal 5'-phosphate : The monophosphate ester obtained by condensation of phosphoric acid with the primary hydroxy group of pyridoxal.

Research Excerpts

ExcerptRelevanceReference
" This regimen was introduced in the 1970s and has remained largely unchanged even though the initial NAC infusion is frequently associated with adverse reactions, in particular nausea, vomiting, and anaphylactoid reactions."2.90Randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with the 12-h regimen of N-acetylcysteine for paracetamol overdose-the PP100-01 for Overdose of Paracetamol (POP) trial: study protocol for a randomi ( Dear, J, 2019)
" Primary endpoints: all participants experienced ≥1 adverse event (AE), most commonly gastrointestinal."2.90Principal results of a randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with a 12 h regimen of N-acetylcysteine for paracetamol overdose (POP trial). ( Black, P; Dear, JW; Gallagher, B; Grahamslaw, J; Henriksen, D; Lee, RJ; Morrison, EE; O'Brien, R; Oatey, K; Oosthuyzen, W; Weir, CJ, 2019)
"Fomepizole (4-methylpyrazole) is safe and has shown efficacy in preclinical models, human hepatocytes and in volunteers against APAP overdose."2.66Novel strategies for the treatment of acetaminophen hepatotoxicity. ( Akakpo, JY; Jaeschke, H; Ramachandran, A, 2020)
"After carbon tetrachloride poisoning the enzyme activity in the plasma increased within 2 h but was not enhanced by pyridoxal 5'-phosphate."1.26Changes in activation of aspartate aminotransferase by pyridoxal 5'-phosphate after experimental liver damage in rabbits. ( Barnard, HC; de Waal, A; le Roux, S; Potgieter, GM; Schoombie, EM, 1982)

Research

Studies (11)

TimeframeStudies, this research(%)All Research%
pre-19906 (54.55)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's4 (36.36)24.3611
2020's1 (9.09)2.80

Authors

AuthorsStudies
Fourches, D1
Barnes, JC1
Day, NC1
Bradley, P1
Reed, JZ1
Tropsha, A1
Akakpo, JY1
Ramachandran, A1
Jaeschke, H1
Dear, J1
Morrison, EE1
Oatey, K1
Gallagher, B1
Grahamslaw, J1
O'Brien, R1
Black, P1
Oosthuyzen, W1
Lee, RJ1
Weir, CJ1
Henriksen, D1
Dear, JW1
Tarrant, J1
Meyer, D1
Katavolos, P1
ITO, F1
YAMAMURA, Y1
HAYANO, K1
de Waal, A1
le Roux, S1
Potgieter, GM1
Barnard, HC1
Schoombie, EM1
Ludwig, S1
Kaplowitz, N1
Young, SW1
Simpson, BB1
Ratner, AV1
Matkin, C1
Carter, EA1
Yoshida, I1
Sakaguchi, Y1
Nakano, M1
Yamashita, F1
Hitoshi, T1

Clinical Trials (1)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Randomised Open Label Exploratory, Safety and Tolerability Study With PP100-01 in Patients Treated With the 12-hour Regimen of N-Acetylcysteine for Paracetamol/Acetaminophen Overdose (The POP Trial)[NCT03177395]Phase 124 participants (Actual)Interventional2017-06-08Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

ALT(U/L)

The alanine aminotransferase (ALT) test is a blood test that checks for liver damage. (NCT03177395)
Timeframe: 10 hours

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)41.4
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC22.9
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC25.3
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC15.0

ALT(U/L)

The alanine aminotransferase (ALT) test is a blood test that checks for liver damage. (NCT03177395)
Timeframe: 20 hours

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)43.3
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC20.4
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC25.4
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC16.4

ALT(U/L)

The alanine aminotransferase (ALT) test is a blood test that checks for liver damage. (NCT03177395)
Timeframe: Baseline

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)42.5
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC24.6
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC29.4
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC17.7

ccK18 (U/L)

Caspace-cleaved Keratin-18 (NCT03177395)
Timeframe: Ratio - value at 20 hours divided by baseline value for each patient

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)2.22
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC1.49
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC1.02
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC1.08

ccK18 (U/L)

The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death). (NCT03177395)
Timeframe: 10 hours

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)72
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC53
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC56
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC78

ccK18 (U/L)

The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death). (NCT03177395)
Timeframe: 20 hours

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)149
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC66
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC85
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC111

ccK18 (U/L)

The shorter, Caspase cleaved form of K-18 is released following hepatocyte apoptosis (programmed cell death). (NCT03177395)
Timeframe: Baseline (2 hours)

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)67
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC45
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC84
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC104

INR

international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF) (NCT03177395)
Timeframe: 10 hours

Interventionratio (Mean)
Acetylcysteine (N-acetylcysteine; NAC)1.30
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC1.17
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC1.20
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC1.22

INR

international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF) (NCT03177395)
Timeframe: 20 hours

Interventionratio (Mean)
Acetylcysteine (N-acetylcysteine; NAC)1.18
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC1.07
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC1.08
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC1.22

INR

international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF) (NCT03177395)
Timeframe: Baseline

Interventionratio (Mean)
Acetylcysteine (N-acetylcysteine; NAC)1.02
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC1.00
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC0.98
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC1.05

INR

international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF) (NCT03177395)
Timeframe: value at 20 hours divided by baseline value for each patient

Interventionratio (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)1.15
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC1.07
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC1.10
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC1.10

K18 (U/L)

In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death. (NCT03177395)
Timeframe: 20 hours

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)347
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC229
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC172
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC181

K18 (U/L)

In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death. (NCT03177395)
Timeframe: Baseline (2 hours)

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)187
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC177
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC193
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC128

K18 (U/L)

In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death. (NCT03177395)
Timeframe: Ratio - value at 20 hours divided by baseline value for each patient

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)1.85
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC1.29
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC0.89
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC1.41

K18(U/L)

In paracetamol overdose, the full-length variant of Keratin-18 (K-18) is released by necrotic hepatocyte death. (NCT03177395)
Timeframe: 10 hours

InterventionU/L (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)182
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC152
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC170
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC111

miR-122 (Copies/mcL)

MiR-122 is a biomarker specific for liver injury and fully conserved (translational) across in vitro models, in vivo models and humans. MiR-122 is an early marker for acute liver injury which predicts a rise in ALT activity following paracetamol overdose (NCT03177395)
Timeframe: 20 hours

Interventioncopies/mcL (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)216,256
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC57,664
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC202,271
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC40,745

miR-122 (Copies/mcL)

MiR-122 is a biomarker specific for liver injury and fully conserved (translational) across in vitro models, in vivo models and humans. MiR-122 is an early marker for acute liver injury which predicts a rise in ALT activity following paracetamol overdose (NCT03177395)
Timeframe: Baseline (2 h)

Interventioncopies/mcL (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)146,363
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC116,749
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC194,075
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC36,051

miR-122 (Copies/mcL)

MiR-122 is a biomarker specific for liver injury and fully conserved (translational) across in vitro models, in vivo models and humans. MiR-122 is an early marker for acute liver injury which predicts a rise in ALT activity following paracetamol overdose (NCT03177395)
Timeframe: Ratio - value at 20 hours divided by baseline value for each patient

Interventioncopies/mcL (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)1.48
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC0.49
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC1.04
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC1.13

miR-122 (Delta Count)

MiR-122 is a biomarker specific for liver injury and fully conserved (translational) across in vitro models, in vivo models and humans. MiR-122 is an early marker for acute liver injury which predicts a rise in ALT activity following paracetamol overdose (NCT03177395)
Timeframe: 10 hours

InterventionDCt (Mean)
Acetylcysteine (N-acetylcysteine; NAC)5.41
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC6.14
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC5.01
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC9.00

miR-122 (Delta Count)

MiR-122 is a biomarker specific for liver injury and fully conserved (translational) across in vitro models, in vivo models and humans. MiR-122 is an early marker for acute liver injury which predicts a rise in ALT activity following paracetamol overdose (NCT03177395)
Timeframe: 20 hours

InterventionDCt (Mean)
Acetylcysteine (N-acetylcysteine; NAC)4.85
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC7.12
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC4.49
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC8.44

miR-122 (Delta Count)

MiR-122 is a biomarker specific for liver injury and fully conserved (translational) across in vitro models, in vivo models and humans. MiR-122 is an early marker for acute liver injury which predicts a rise in ALT activity following paracetamol overdose (NCT03177395)
Timeframe: Baseline (2 hours)

InterventionDCt (Mean)
Acetylcysteine (N-acetylcysteine; NAC)5.58
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC5.85
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC4.43
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC8.73

miR-122(Copies/mcL)

MiR-122 is a biomarker specific for liver injury and fully conserved (translational) across in vitro models, in vivo models and humans. MiR-122 is an early marker for acute liver injury which predicts a rise in ALT activity following paracetamol overdose (NCT03177395)
Timeframe: 10 hours

Interventioncopies/mcL (Geometric Mean)
Acetylcysteine (N-acetylcysteine; NAC)206,205
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC109,882
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC196,732
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC37,066

Additional NAC Infusion

participants required additional NAC infusions after the 12-hour NAC regimen (NCT03177395)
Timeframe: Additional NAC at 12 hour

,,,
InterventionParticipants (Count of Participants)
NoneOneTwo
Acetylcysteine (N-acetylcysteine; NAC)312
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC510
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC600
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC600

Safety Events

Adverse Events and Serious Adverse Events (NCT03177395)
Timeframe: 90 days

,,,
Interventionparticipants (Number)
Any Adverse eventAny serious adverse eventAdverse event after commencement of NAC treatmentSerious AE after commencement of NAC treatmentAdverse event where outcome was deathAdverse event unrelated to NACAdverse event possibly related to NACAdverse event probably related to NACAdverse event definitely related to NACAdverse event unrelated to PP100-01Adverse event possibly related to PP100-01Adverse event probably related to PP100-01Adverse event definitely related to PP100-01Any suspected unexpected serious adverse reactionSUSAR to NACSUSAR to PP100-01SUSAR to NAC and PP100-01
Acetylcysteine (N-acetylcysteine; NAC)62610323260000000
Group A: PP100-01 (Calmangafodipir 2 Umol/kg)+ NAC64510522364000000
Group B: PP100-01 (Calmangafodipir 5 Umol/kg)+ NAC62611323152000000
Group C: PP100-01 (Calmangafodipir 10 Umol/kg)+ NAC63620522162001010

Reviews

3 reviews available for pyridoxal phosphate and Acute Liver Injury, Drug-Induced

ArticleYear
Novel strategies for the treatment of acetaminophen hepatotoxicity.
    Expert opinion on drug metabolism & toxicology, 2020, Volume: 16, Issue:11

    Topics: Acetaminophen; Acetylcysteine; Animals; Antidotes; Chemical and Drug Induced Liver Injury; Drug Over

2020
Use of optimized aminotransferase methods in regulated preclinical studies.
    Veterinary clinical pathology, 2013, Volume: 42, Issue:4

    Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Biomarkers; Chemical and Drug Induced Li

2013
Pyridoxine and its metabolism in chronic liver disease.
    Nutrition reviews, 1977, Volume: 35, Issue:6

    Topics: Alcoholism; Chemical and Drug Induced Liver Injury; Chronic Disease; Humans; Liver; Liver Diseases;

1977

Trials

2 trials available for pyridoxal phosphate and Acute Liver Injury, Drug-Induced

ArticleYear
Randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with the 12-h regimen of N-acetylcysteine for paracetamol overdose-the PP100-01 for Overdose of Paracetamol (POP) trial: study protocol for a randomi
    Trials, 2019, Jan-08, Volume: 20, Issue:1

    Topics: Acetaminophen; Acetylcysteine; Chemical and Drug Induced Liver Injury; Clinical Trials Data Monitori

2019
Principal results of a randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with a 12 h regimen of N-acetylcysteine for paracetamol overdose (POP trial).
    EBioMedicine, 2019, Volume: 46

    Topics: Acetaminophen; Acetylcysteine; Adult; Biomarkers; Chemical and Drug Induced Liver Injury; Drug Inter

2019

Other Studies

6 other studies available for pyridoxal phosphate and Acute Liver Injury, Drug-Induced

ArticleYear
Cheminformatics analysis of assertions mined from literature that describe drug-induced liver injury in different species.
    Chemical research in toxicology, 2010, Volume: 23, Issue:1

    Topics: Animals; Chemical and Drug Induced Liver Injury; Cluster Analysis; Databases, Factual; Humans; MEDLI

2010
THE FATTY LIVER INDUCTION OF ALPHA-ETHYLTHIOISONICOTINAMIDE (ETHIONIAMIDE, 1314TH).
    Journal of biochemistry, 1964, Volume: 55

    Topics: Chemical and Drug Induced Liver Injury; Choline; Ethionamide; Fatty Liver; Hepatitis; Nucleosides; P

1964
Changes in activation of aspartate aminotransferase by pyridoxal 5'-phosphate after experimental liver damage in rabbits.
    Clinica chimica acta; international journal of clinical chemistry, 1982, Jul-15, Volume: 122, Issue:3

    Topics: Animals; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Live

1982
Effect of pyridoxine deficiency on serum and liver transaminases in experimental liver injury in the rat.
    Gastroenterology, 1980, Volume: 79, Issue:3

    Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Bromobenzenes; Chemical and Drug Induced

1980
MRI measurement of hepatocyte toxicity using the new MRI contrast agent manganese dipyridoxal diphosphate, a manganese/pyridoxal 5-phosphate chelate.
    Magnetic resonance in medicine, 1989, Volume: 10, Issue:1

    Topics: Animals; Chemical and Drug Induced Liver Injury; Contrast Media; Edetic Acid; Ethanol; Galactosamine

1989
Pyridoxal phosphate-induced liver injury in a patient with homocystinuria.
    Journal of inherited metabolic disease, 1985, Volume: 8, Issue:2

    Topics: Chemical and Drug Induced Liver Injury; Child; Homocystinuria; Humans; Male; Pyridoxal Phosphate

1985