Cytochrome P450 Enzymes and Transporters Induced by Anti-Human Immunodeficiency Virus Protease Inhibitors in Human Hepatocytes: Implications for Predicting Clinical Drug Interactions

Dixit, Vaishali; Hariparsad, Niresh; Li, Fang; Desai, Pankaj B.; Thummel, Kenneth E.; Unadkat, Jashvant D.

doi:10.1124/dmd.107.016089

Cited by 129 publications

(111 citation statements)

References 32 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…The relationship between breast cancer and the CYP gene family was recently reported, including CYP1B1 (Economopoulos and Sergentanis, 2010;Ozbek et al, 2010), CYP2J2 (Jiang et al, 2007(Jiang et al, , 2009), CYP2D6 (Stingl et al, 2010;González-Tejera et al, 2010;Thompson et al, 2011), CYP2C8 (Knüpfer et al, 2004;Dixit, et al, 2007;Jernström et al, 2009), CYP2C9 (Ekhart et al, 2008;Jernström et al, 2009) and CYP2C19 (Justenhoven et al, 2009;Ruiter et al, 2010;Goetz and Suman, 2010). Several studies have reported different conclusions for the relationship with CYP2C19.…”

Section: Discussionmentioning

confidence: 99%

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Gan¹,

Wang²,

Cao³

et al. 2011

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. Cytochrome P450 (CYP) 2C19 metabolizes arachidonic acid to biologically active epoxyeicosatrienoic acids, which significantly promote proliferation of cancer cells in vitro and in vivo. We looked for a possible association between human CYP2C19*3 gene polymorphism and breast cancer in the Chinese Han population. In a Chinese Han case-control study of breast cancer patients (N = 600) and age-and gender-matched healthy controls (N = 600), we investigated polymorphism in the CYP2C19 gene by PCR-RFLP analysis. The CYP2C19*3 AG + AA genotype was significantly more prevalent in breast cancer patients than in control subjects (6.67 vs 3.00%; P = 0.003). The odds ratio for carriers of AG + AA genotype for breast cancer was 2.31 (95% confidence interval = 1.27-4.43). Among patients, estrogen receptor, tumor size, histologic grade, presence of primary lymphonode metastases, progesterone receptor positivity, and age at diagnosis were not found to be significantly associated with CYP2C19*3 genotypes (all P > 0.05). We conclude that the CYP2C19*3 gene polymorphism is associated with breast cancer risk in Chinese Han women.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Gan¹,

Wang²,

Cao³

et al. 2011

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…in a dose-dependent manner. A 12% decrease of ritonavir exposure is already seen with doses of 400mg daily and exposure further decreased by 45% with ritonavir 1000mg/d [19] An increase of cytochrome 2C9, 2C19 and 1A2 activity by ritonavir was shown in human hepatocytes [15] as well as under long term treatment with lopinavir boosted with 200mg ritonavir daily in healthy volunteers [16]. As CYP2C9 and CYP1A2 are involved in albendazole and albendazole sulfoxide metabolism [22], their induction by long term ritonavir administration of 400mg daily could explain a lower bioavailability of albendazole.…”

Section: Discussionmentioning

confidence: 99%

“…Consequently, interaction of protease inhibitors with drugs that are cleared predominantly by CYP3A enzymes are profound and clinically significant [14]. It is still equivocal whether long-term administration of ritonavir may also lead to a certain induction of CYP3A enzymes [15]. However, studies both in healthy volunteers [16] and patients [17] do not support CYP3A4 induction.…”

Section: Introductionmentioning

confidence: 99%

Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers

Corti

Heck

Rentsch

et al. 2009

Eur J Clin Pharmacol

View full text Add to dashboard Cite

Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers Abstract BACKGROUND: Benzimidazoles are often used concomitantly with protease inhibitors in patients with helminthic disease and HIV infection. Low bioavailability and extensive first-pass metabolism make benzimidazoles prone to pharmacokinetic drug interactions. The aim of the present study was to investigate potential drug interactions between the benzimidazoles albendazole and mebendazole and the potent CYP3A4 inhibitor ritonavir. METHODS: Sixteen healthy volunteers were administered a single oral dose of 1,000 mg mebendazole or 400 mg albendazole (2 x n = 8). AUC, C(max), and t(1/2) of mebendazole, albendazole, and albendazole sulfoxide were studied in absence and after short-term (2 doses) and long-term (8 days) treatment with ritonavir 200 mg bid. RESULTS: Pharmacokinetic parameters of albendazole and mebendazole were not changed by short-term administration of ritonavir. However, long-term administration of ritonavir resulted in significant changes in albendazole and mebendazole disposition, with a significant decrease in AUC(0-24) (27 and 43% of baseline for albendazole and mebendazole, respectively) and C(max) (26 and 41% of baseline, respectively). CONCLUSION: The AUC(0-24) of benzimidazoles decreased after long-term use of ritonavir, while no changes in pharmacokinetic profiles were observed under short-term administration. These findings might help to optimize benzimidazole efficacy when used in combination with protease inhibitors.

show abstract

“…Protease inhibitors are metabolised by the cytochrome P450 system. They may inhibit or induce the system and alter the [61]. Indeed, paclitaxel exposure (the area under curve) is increased in patients receiving protease inhibitors.…”

Section: Differential Diagnosismentioning

confidence: 99%

Pulmonary manifestations of human herpesvirus-8 during HIV infection

et al. 2013

View full text Add to dashboard Cite

Human herpesvirus (HHV)-8 is an oncogenic gamma herpesvirus that was first described in 1994 in Kaposi sarcoma lesions. HHV-8 is involved in the pathophysiological features of multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL), both rare B-cell lymphoproliferative diseases. HHV-8-related tumours occur almost exclusively in immunocompromised patients, mostly those with HIV infection. Combined antiretroviral therapies have reduced the incidence of Kaposi sarcoma but not MCD and PEL.HHV-8-related diseases frequently exhibit pulmonary involvement, which may indicate the disease. Kaposi sarcoma in the lung is often asymptomatic but may require specific therapy. It mostly shows cutaneous or mucosal involvement. Patients with typical MCD present fever and lymphadenopathy associated with interstitial lung disease without opportunistic infection. Specific treatment may be urgent. PEL provokes a febrile, lymphocytic-exudative pleural effusion, without a pleural mass on computed tomography scan. Rapid diagnosis prevents unnecessary examinations and leads to specific, rapid treatment. Therapy is complex, combining antiretroviral therapy and chemotherapy. @ERSpublications HHV-8-related diseases frequently exhibit pulmonary involvement, which may indicate the disease

show abstract

Cytochrome P450 Enzymes and Transporters Induced by Anti-Human Immunodeficiency Virus Protease Inhibitors in Human Hepatocytes: Implications for Predicting Clinical Drug Interactions

Cited by 129 publications

References 32 publications

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Association of CYP2C19*3 gene polymorphism with breast cancer in Chinese women

Effect of ritonavir on the pharmacokinetics of the benzimidazoles albendazole and mebendazole: an interaction study in healthy volunteers

Pulmonary manifestations of human herpesvirus-8 during HIV infection

Contact Info

Product

Resources

About