Influence of Age-Dependent Pharmacokinetics and Metabolism on Acetaminophen Hepatotoxicity

Rumore, Martha M.; Blaiklock, Robert G.

doi:10.1002/jps.2600810302

Cited by 33 publications

(13 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neonates are capable of metabolising APAP, not by glucuronidation but also by sulphation,11 22 27 and there is no correlation with plasma bilirubin concentration 22…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates

Lingen

Deinum

Quak

et al. 1999

Archives of Disease in Childhood - Fetal and Neonatal Edition

129

View full text Add to dashboard Cite

Aim-To investigate the pharmacokinetics, metabolism, and dose-response relation of a single rectal dose of paracetamol in preterm infants in two diVerent age groups. Methods-Preterm infants stratified by gestational age groups 28-32 weeks (group 1) and 32-36 weeks (group 2) undergoing painful procedures were included in this study. Pain was assessed using a modified facies pain score. Results-Twenty one infants in group 1 and seven in group 2 were given a single rectal dose of 20 mg/kg body weight. Therapeutic concentrations were reached in 16/21 and 1/7 infants in groups 1 and 2, respectively. Peak serum concentrations were significantly higher in group 1. Median time to reach peak concentrations was similar in the two groups. As serum concentration was still in the therapeutic range for some infants in group 1, elimination half life (T 1 ⁄2) could not be determined in all infants: T 1 ⁄2 was 11.0 ± 5.7 in 11 infants in group 1 and 4.8 ± 1.2 hours in group 2. Urinary excretion was mainly as paracetamol sulphate. The glucuronide:sulphate ratio was 0.12 ± 0.09 (group 1) and 0.28 ± 0.35 (group 2). The pain score did not correlate with therapeutic concentrations. Conclusions-A 20 mg/kg single dose of paracetamol can be safely given to preterm infants in whom sulphation is the major pathway of excretion. Multiple doses in 28-32 week old neonates would require an interval of more than 8 hours to prevent progressively increasing serum concentrations. (Arch Dis Child Fetal Neonatal Ed 1999;80:F59-F63)

show abstract

“…Neonates are capable of metabolising APAP, not by glucuronidation but also by sulphation,11 22 27 and there is no correlation with plasma bilirubin concentration 22…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates

Lingen

Deinum

Quak

et al. 1999

Archives of Disease in Childhood - Fetal and Neonatal Edition

129

View full text Add to dashboard Cite

show abstract

“…When all data were normalised to the body surface area, however, the differences disappeared. The authors felt that this general phenomenon accounted for the requirement of much higher doses in young children to attain the same blood concentrations.l 1l3 ] Rumore and Blaiklock [114] addressed the issue of why plasma concentrations of paracetamol that are clearly toxic in adults are well tolerated and rarely fatal in children under age 6 years. They observed that the pattern of metabolism in children is to excrete 50% of the drug as the sulphate conjugate and only 18% as the glucuronide, whereas in adults glucuronide conjugates account for 55% of the metabolites and sulphate only 27%.…”

Section: Lessons From Paediatricsmentioning

confidence: 99%

Age-Related Changes in the Gastrointestinal System

1994

View full text Add to dashboard Cite

Although there are many changes in the gastrointestinal tract with aging, only those in the liver substantially influence blood concentrations and clearance of drugs. The liver mass, overall function, and blood flow decrease approximately 1% per year after age 40 to 50 years, and accordingly, the hepatic metabolism or clearance of drugs decreases in this proportion. The sensitivity of the gastrointestinal tract to usual concentrations of drugs is increased, and this, in part, accounts for the increased frequency of adverse drug reactions in elderly patients.

show abstract

“…In general, acetaminophen is a safe agent; however, excessive short-term doses (1 15 g in an adult) or long-term use (> 5 g/day) can cause hepatotoxicity (Table 1) . [21][22][23][24][25][26][27][28][29][30][31][32][33] In addition, evidence suggests that long-term ingestion of ethanol may predispose individuals to acetaminophen-related h e p a t o t o x i~i t y .~~. 35 Concern was raised regarding the potential for acetaminophen-induced hepatotoxicity after modest doses (4-10 g/24 hrs) during fasting conditions (e.g., viral illness with gastrointestinal symptoms, dehydration) .…”

Section: Acetaminophenmentioning

confidence: 99%

“…22 The NSAIDs appear to have a ceiling for analgesic effect beyond which a dosage increase does not provide increased relief. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] Because this ceiling varies from patient to patient, slow dosage escalation can help determine this value. 36 Patients may respond differently to certain agents; therefore, a trial with another NSAID may be appropriate if the first one provides inadequate pain relief.37…”

Section: Nsaidsmentioning

confidence: 99%

Safety Issues in the Pharmacologic Management of Chronic Pain in the Elderly

Shimp

1998

Pharmacotherapy

View full text Add to dashboard Cite

Chronic pain is commonly encountered in elderly patients. About 20–50% of community‐dwelling elderly experience it, and 45–80% of nursing home residents may be affected. Selection of pharmacologic therapy for the management of chronic pain must take into consideration the increased potential for adverse effects in this population. Major classes of drugs used to treat chronic pain (nonsteroidal antiinflammatory drugs, opioids, antidepressants) have adverse effects that occur more frequently in elderly than in younger patients. Given the often prolonged duration of therapy, optimal management requires minimizing the risk of adverse reactions.

show abstract

Influence of Age-Dependent Pharmacokinetics and Metabolism on Acetaminophen Hepatotoxicity

Cited by 33 publications

References 37 publications

Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates

Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates

Age-Related Changes in the Gastrointestinal System

Safety Issues in the Pharmacologic Management of Chronic Pain in the Elderly

Contact Info

Product

Resources

About