Cytochrome P-450 3A: Interactions with dermatologic therapies

Singer, M. I. C.; Shapiro, Lori E.; Shear, Neil H.

doi:10.1016/s0190-9622(97)70115-4

Cited by 55 publications

(17 citation statements)

References 15 publications

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“…SU5416 is metabolized via the cytochrome P-450 liver enzyme, CYP1A2 (an inducible enzyme), and to a lesser extent, by CYP3A4, CYP2C9, and CYP2C19. Patients receiving drugs and agents that inhibit or induce this enzyme, including some antifungal agents (45) and macrolide antibiotics (46), may have altered plasma levels of SU5416. Recent data suggest that beverages such as coffee and grapefruit juice also inhibit CYP3A (47).…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma

Zangari

Anaissie

Stopeck

et al. 2004

Clinical Cancer Research

109

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Purpose: Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with multiple myeloma (MM). VEGF, a soluble circulating angiogenic molecule, acts via receptor tyrosine kinases, including VEGF receptor 2. SU5416 is a small molecule VEGF receptor 2 inhibitor.Experimental Design: Adult patients with advanced MM were entered on a multicenter phase II study.Results: Twenty-seven patients (median age 69, range 39 -79), median 4 (0 -10) lines of prior therapy, 14 with prior thalidomide therapy, received SU5416 at 145 mg/m 2 twice weekly i.v. for a median of two 4-week cycles (range 0.2-9). Grade 3/4 toxicities were rarely observed; the most frequent was thrombocytopenia (12%). Mild-to-moderate toxicities included nausea (63%), headache (56%), diarrhea, vomiting (both 37%), and fatigue (33%). There were three thromboembolic episodes and five cases of new onset hypertension. Two (7%) patients did not complete the first 4-week cycle of therapy because of adverse events (pneumonia and headache). There were no objective responses. Four patients had disease stabilization for >4 months. A decrease in median VEGF plasma levels was observed in patients with stable disease (n ‫؍‬ 7) compared with patients with progressive disease (n ‫؍‬ 5). Overall median survival was 42 weeks (range 3-92؉).Conclusions: Although SU5416 had minimal clinical activity, signs of biological activity (decrease in plasma VEGF levels) suggest that angiogenic modulation may be of value in patients with MM.

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Section: Patients Materials and Methodsmentioning

confidence: 99%

Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma

Zangari

Anaissie

Stopeck

et al. 2004

Clinical Cancer Research

109

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“…It is thought that predisposed patients might be unable to detoxify areneoxide metabolites of antiepileptic drugs adequately, initiating an autoimmune attack on the target organs where the cytochrome P-450 system is produced. It has also been proposed that the antiepileptic drug mimics viral infection by activating CD4+ and CD8+ T cells, with the concomitant production of interleukin-5, the main maturation factor for eosinophils [9].…”

Section: Discussionmentioning

confidence: 99%

Anticonvulsant Hypersensitivity Syndrome: Report of 2 Cases from Kuwait

Bin-Nakhi

Sadeq²,

Pinto³

et al. 2003

Med Princ Pract

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Objective: To illustrate the clinical features, laboratory findings, and management of anticonvulsant hypersensitivity syndrome (AHS), emphasizing the importance of recognizing its multiple clinical components and raising awareness of the cross-sensitivity among different anticonvulsants. Clinical Presentation and Intervention: Two cases of AHS due to carbamazepine and a combination of sodium valproateand lamotrigene are reported. Both patients presented within the first month of starting the new antiepileptic medication with fever, skin rashes, hematological abnormalities, and hepatitis. The offending antiepileptic drugs were immediately stopped in both cases. Skin rashes responded to intravenous immunoglobulin in case 1 and to intravenous hydrocortisone in case 2. Conclusion: AHS is a serious, life-threatening condition. This report demonstrates that the most important steps in the management of AHS are to recognize the disorder, discontinue the offending antiepileptic drug, and provide supportive care in an inpatient setting and treat with benzodiazepines if seizures occur.

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“…This processing is divided into categories of Phase 1 and Phase 2 metabolism: Phase 1 metabolism results in molecular changes through oxidation, reduction, or hydrolysis to incorporate a polar reactive group; Phase 2 metabolism contributes ''extramolecular changes'' to the metabolic products of Phase I through conjugation with glucuronide, sulfate, glutathione, methyl, or acetyl groups (see Fig. 1) (2,3). Note that metabolites may be prepared to be excreted after Phase 1 alone.…”

Section: Drug Metabolism and The Cytochrome P450 Enzyme Familymentioning

confidence: 99%

“…Cutaneous CYP enzyme expression was described more than 20 years ago (6). The enzyme family is named for a shared hemoprotein that produces a spectral absorbance maximum at 450 nm when bound to carbon monoxide and subclassified based on spectral properties, molecular masses, substrate selectivity, and immunoreactivities (2,7).…”

Section: Drug Metabolism and The Cytochrome P450 Enzyme Familymentioning

confidence: 99%

Polymorphic Cytochrome P450 Enzymes and Post-Marketing Drug Dosage Revisions: Clinical Relevance to Dermatologic Therapies

Saggar

Maibach

2007

Cutaneous and Ocular Toxicology

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The therapeutic drug resources available to dermatologists have expanded and encompass off-label use of other drugs as well. As these new resources are employed, it is important to remain vigilant of possible drug interactions and toxicities contingent upon inter-individual variability of plasma drug levels. This article reviews the biochemistry of CYP enzymes and the clinical implications of genetic polymorphisms as relating to certain dermatologic drugs. In addition, we discuss the potential clinical function of cutaneous CYP enzymes.

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Cytochrome P-450 3A: Interactions with dermatologic therapies

Cited by 55 publications

References 15 publications

Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma

Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma

Anticonvulsant Hypersensitivity Syndrome: Report of 2 Cases from Kuwait

Polymorphic Cytochrome P450 Enzymes and Post-Marketing Drug Dosage Revisions: Clinical Relevance to Dermatologic Therapies

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