Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Saquinavir, a potent human immunodeficiency virus protease inhibitor, is extensively metabolized by CYP3A4. Saquinavir is coadministered with ritonavir, a strong CYP3A4 inhibitor, to boost its exposure. Ketoconazole is a potent CYP3A inhibitor. The objectives of this study were to investigate the effect of ketoconazole on the pharmacokinetics of saquinavir/ritonavir and vice versa using the approved dosage regimens of saquinavir/ritonavir at 1,000/100 mg twice daily and ketoconazole at 200 mg once daily. This was an open-label, randomized two-arm, one-sequence, two-period crossover study in healthy subjects. In study arm 1, 20 subjects received saquinavir/ritonavir treatment alone for 14 days, followed in combination with ketoconazole treatment for 14 days. In arm 2, 12 subjects received ketoconazole treatment for 6 days, followed in combination with saquinavir/ritonavir treatment for 14 days. The pharmacokinetics were assessed on the last day of each treatment (days 14 and 28 in arm 1 and days 6 and 20 in arm 2). The exposures C(max) and the area under the concentration-time curve from 0 to 12 h (AUC(0-12)) of saquinavir and ritonavir with or without ketoconazole were not substantially altered after 2 weeks of concomitant dosing with ketoconazole. The C(max) and AUC(0-12) of ketoconazole, dosed at 200 mg once daily, were increased by 45% (90% confidence interval = 32 to 59%) and 168% (90% confidence interval = 146 to 193%), respectively, after 2 weeks of concomitant dosing with ritonavir-boosted saquinavir (1,000 mg of saquinavir/100 mg of ritonavir given twice daily). The greater exposure to ketoconazole when given in combination with saquinavir/ritonavir was not associated with unacceptable safety or tolerability. No dose adjustment for saquinavir/ritonavir (1,000/100 mg twice daily) is required when coadministered with 200 mg of ketoconazole once daily, and high doses of ketoconazole (>200 mg/day) are not recommended.
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PMID:Drug-drug interaction study of ketoconazole and ritonavir-boosted saquinavir. 1901 29

A 34-year-old nonpregnant woman noted a mildly pruritic skin lesion on her right breast for 1 week following an episode of coryza, malaise, and low-grade fever of 3 days' duration. The latter symptoms subsided without any treatment. Ketoconazole cream prescribed by her family physician did not resolve the breast eruption after 1 week, so was stopped. A week later, multiple skin lesions erupted suddenly on her right chest wall starting near the herald patch in midaxillary line and spread distally until the midback. She then consulted the authors. She denied a history of abrasion or trauma to the affected areas. Travel, contact, sexual, and drug histories were unremarkable. She categorically denied past or family history of eczema, psoriasis, contact dermatitis, and drug eruptions. On examination, the initial lesion was an annular and well-demarcated erythematous plaque on her right breast in the upper outer quadrant. Multiple small oval scaly plaques were noted, extending distally along the ribs to the midline on her back, not crossing the midline, predominantly over the distribution of right T4 dermatome (Figure 1). Peripheral collarette scaling was noted (Figure 2). A few scattered small lesions were also noted in the vicinity of this dermatome. Three isolated small plaques were also present on the trunk, one in the supramammary area and the other two on the abdomen and back, respectively. Palmoplantar and mucosal surfaces were uninvolved. The rest of the skin and systemic examination revealed no abnormalities. Complete blood cell counts, fasting glucose, and urinalysis were normal. Venereal Disease Research Laboratory (VDRL) results were nonreactive and human immunodeficiency virus (HIV) antibodies were negative. Repeat testing ofVDRL in serial dilutions and HIV antibodies after 3 months were also nonreactive and negative, respectively. Scrapings from the initial large lesion and subsequent smaller eruptions did not show any evidence of fungal infection on potassium hydroxide smear examination. The patient declined skin biopsy; however, we thought that the most diagnostic label for this condition was pityriasis rosea. Hence, we treated her with triamcinolone acetonide ointment 0.025% to be applied twice daily and desloratadine tablet 5 mg daily for 10 days. The patient demonstrated complete resolution, leaving postinflammatory hypopigmentation. There was no recurrence until 1 year after complete remission.
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PMID:Segmental lesions in pityriasis rosea: a rare presentation. 2225 28

This case study presents an unusual pathogenic association among several cranioencephalic lesions characterized by the association of osteitis of the cranial vault, due to Aspergillus fumigatus, with underlying thrombophlebitis complicated by intracranial hypertension resulting from hydrocephalus. The study involved a 43-year old HIV (human immunodeficiency virus) negative man with multi-recurrent infection of the frontal scalp. The patient was successfully treated with cerebrospinal fluid diversion (CFD), Ketoconazole and low molecular weight heparin. This study describes the different pathophysiological and therapeutic features of this exceptional pathogenic association.
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PMID:[Hydrocephaly resulting from thrombophlebitis of the superior sagittal sinus due to osteitis of the cranial vault caused by Aspergillus fumigatus in an immunocompetent patient]. 3101 98


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