Glucuronidation and sulphation of paracetamol in HIV‐positive patients and patients with AIDS

O’Neil,; Pezzullo,; Girolamo, Di; Tsoukas,; Wainer, Gabriel

doi:10.1046/j.1365-2125.1999.00084.x

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…It was reported that if acetaminophen and salicylamide were administered together to human subjects, the sulfonation rate of each substrate was lower than when the compounds were administered individually [142]. In another clinical study, dapsone was found to significantly decrease the sulfonation of acetaminophen [143].…”

Section: Therapeutic Drugsmentioning

confidence: 97%

“…It was shown that the central region spanning amino acid residues 102-164 in rat hydroxysteroid SULT are essential for the activity [52]. Studies using (HUMAN)SULT1A1 and 1A3, which are 93% identical but exhibit distinct substrate specificity and other enzymatic properties, have revealed that region I (84)(85)(86)(87)(88)(89) and region II (143)(144)(145)(146)(147)(148) were responsible for its substrate specificity [53]. A chimeric construct of (HUMAN)SULT 1A1 with region I replaced with region II showed (HUMAN) SULT1A3 specificity, and vice versa [53].…”

Section: Structure Of Sultsmentioning

confidence: 98%

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Inhibition of Sulfotransferases by Xenobiotics

Wang

James²

2006

CDM

132

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The sulfotransferase (SULT) family comprises important phase II conjugation enzymes for the detoxification of xenobiotics and modulation of the activity of physiologically important endobiotics such as thyroid hormones, steroids, and neurotransmitters. SULT enzymes catalyze the transfer of a sulfuryl group, donated by 3'-phosphoadenosine-5'-phosphosulfate (PAPS), to an acceptor substrate that may be a hydroxy group or an amine group in a process originally called sulfation, but more correctly referred to as sulfonation or sulfurylation. SULT activity may be inhibited when humans are exposed to certain xenobiotics including drugs (mefenamic acid, salicylic acid, clomiphene, danazol etc.), dietary chemicals (catechins, food colorants, flavonoids and phytoestrogens etc.), and environmental chemicals (hydroxylated polychlorinated biphenyls, hydroxylated polyhalogenated aromatic hydrocarbons, pentachlorophenol, triclosan and bisphenol A, etc.). Inhibition of individual SULT isoforms may cause adverse effects on human health. For example, hydroxylated polychlorinated biphenyls have been shown to interfere with the transport of thyroid hormones, inhibit estradiol sulfonation, and inhibit thyroid hormone sulfonation, thereby potentially disrupting the thyroid hormone system. Formation of sulfate conjugates of toxic xenobiotics usually decreases their toxicity, so inhibition of this pathway may lead to prolonged exposure to the compounds. Conversely, some sulfate conjugates are chemically reactive, inhibition of their formation may protect from toxicity. This manuscript will review the literature concerning the inhibition of SULTs by xenobiotics including isoform-selective effects, inhibition kinetics and health effects resulting from the inhibition.

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Section: Therapeutic Drugsmentioning

confidence: 97%

Section: Structure Of Sultsmentioning

confidence: 98%

Inhibition of Sulfotransferases by Xenobiotics

Wang

James²

2006

CDM

132

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“…Although the previous mentioned study found a correlation between GSH levels and progression of HIV, other studies have not found a difference. For example, another urine study found that the molar concentrations of APAP and its glucuronide and sulphate metabolites were not associated with disease state in HIV/ AIDS patients versus healthy controls [59]. Some authors conclude that although low GSH levels have been observed in patients with HIV and Hepatitis, there is no convincing evidence that these populations are at higher risk for OD at therapeutic levels [60].…”

Section: Effect Of Hiv On Acetaminophen Metabolismmentioning

confidence: 99%

The Impact of the Drug Overdose Epidemic on the Mortality of Persons with HIV/AIDS

Manini¹

2012

J Clinic Toxicol

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Introduction: In the highly active anti-retroviral therapy (HAART) era, acquired immunodeficiency syndrome (AIDS)-related causes of death have declined, while non-AIDS-related causes, especially drug overdose and liver disease, have become a leading cause of death in persons with human immunodeficiency virus (HIV). Excess mortality among HIV-infected patients has been identified in those with substance use dependence. Our aim was to review the recent literature regarding the impact of HIV/AIDS on the current drug overdose epidemic with respect to the HAART era (1997 onwards). Methods: This systematic review screened Pubmed database using search terms (HIV, AIDS, HAART, overdose, hepatitis, nephropathy, opioid, acetaminophen, methadone) and included cohort studies with derived mortality rates while excluding individual case reports, commentaries, letters, and publications over 20 years old. The crude overdose mortality rate (COMR) for each study was used to calculate a pooled COMR for each region during the post-HAART era. Calculation of 95% confidence intervals (CI) for COMR used 5% alpha. Results: The COMR in HIV-infected persons was calculated for 17 cohort studies that analyzed cause of death in 22,414 total cases of HIV infected individuals who died from overdose in the United States, Canada, Puerto Rico, Europe, and Asia. The COMR worldwide during the pre-HAART era was 4.0% (CI 0.9-7.16) but this figure significantly increased to 17.5% (CI 12.4-22.7) during the post-HAART era. Factors that contributed to the rising COMR included: demographic factors, chronic pain, acetaminophen use, intravenous drug use, prescription drug addiction, HAART use, and end-organ disease (nephropathy, liver disease, neuro-cognitive disorder). Conclusion: In the HAART era, AIDS-related causes of death declined, while deaths due to overdose significantly increased in HIV patients. The rise in COMR was primarily attributable to pharmaceutical drugs for pain management. AIDS-related end-organ diseases may possibly impair metabolism and physiologic responses to drug overdose. Future research should focus on expanded COMR reporting, drug misuse, and prognostic markers. between drug abuse, overdose, and HIV are challenging because of the difficulties in enrollment and retention in the most at-risk populations. As such, clinical research is needed to aggressively seek out high-risk, hard-to-reach substance abusers and to offer them HIV testing, access to treatment, and the necessary support to remain in treatment-both for HIV and for substance abuse [10]. Given the strong co-dependence between the epidemics of HIV/ AIDS and drug overdose, the goals of this systematic review are to assess the impact of HIV/AIDS on the current drug overdose epidemic. Firstly, this review will compare various studies from the United States, Canada, Puerto Rico, Europe, Asia, and Africa that address the impact of overdose on the mortality of HIV positive individuals. Using these studies we will derive an estimate of crude mortality rate due to overdose in HIV...

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“…However, using dapsone as NAT2 probe, the genotype-phenotype discordances were not confirmed [11]. Paracetamol sulfation and glucuronidation were not influenced by the state or progression of HIV infection [12].…”

Section: Introductionmentioning

confidence: 99%