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Fulltext Effects of cytochrome p450 inhibitors on itraconazole and fluconazole induced cytotoxicity in hepatocytes

Somchit N, Ngee CS, Yaakob A, Ahmad Z, Zakaria ZA

J Toxicol, 2009;2009:912320.
PMID: 20130764 DOI: 10.1155/2009/912320

Itraconazole and fluconazole have been reported to induce hepatotoxicity in patients. The present study was designed to investigate the role of cytochrome P450 inhibitors, SKF 525A, and curcumin pretreatment on the cytotoxicity of antifungal drugs fluconazole and itraconazole. For 3 consecutive days, female rats were administered daily SKF 525A or curcumin (5 and 25 mg/kg). Control rats received an equivalent amount of dosed vehicle. The animals were anaesthetized 24 hours after receiving the last dose for liver perfusion. Hepatocytes were then exposed to various concentrations of antifungal drugs. In vitro incubation of hepatocytes with itraconazole revealed significantly lower viability when compared to fluconazole as assessed by lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase activities. The cytotoxicity of itraconazole was enhanced when incubated with hepatocytes pretreated with SKF 525A. SKF 525A had no effects on the cytotoxicity of fluconazole. Curcumin failed to either increase or decrease the cytotoxicity of both antifungal drugs. ATP levels also showed significant decrease in both itraconazole and fluconazole incubated hepatocytes. However, SKF 525A pretreated hepatocytes had significantly lower ATP levels after itraconazole incubations. Collectively, these results confirm the involvement of cytochrome P450 in the cytoprotection in itraconazole induced hepatocyte toxicity. Differences of the effects of SKF 525A on the cytotoxicity induced by itraconazole and fluconazole may be due to the differences on the metabolism of each antifungal drug in vivo.
Fulltext Evaluation of Ocular Surface Disease in Asian Patients with Primary Angle Closure

Ling TE, Othman K, Yan OP, Rashid RA, Tet CM, Yaakob A, et al.

Open Ophthalmol J, 2017;11:31-39.
PMID: 28400889 DOI: 10.2174/1874364101711010031

OBJECTIVE: To evaluate the incidence of ocular surface disease (OSD) and to determine the effects of topical pressure-lowering drugs on ocular surface disease in primary angle closure patients.
METHODS: This was a cross-sectional comparative study comparing primary angle closure glaucoma (PACG) patients (Group A) with primary angle closure and primary angle closure suspect (Group B). Group A was treated with topical pressure-lowering drugs; Group B was not. Data on ocular diagnosis and details of treatment were obtained from medical records. Ocular surface disease incidence was assessed using the Ocular Surface Disease Index (OSDI) questionnaire and from clinical signs using Schirmer's test, tear break-up time and corneal fluorescein stain. Predictive Analytic Software 20 and STATA analysis software were used for statistical analyses.
RESULTS: Group A demonstrated a higher rate of OSD (OSDI 52.3%, Schirmer's test 70.5%, tear break-up time (TBUT) 75%, corneal staining 77.3%) compared to Group B (OSDI 39.0%, Schirmer's test 73.2%, TBUT 58.5% and cornea staining 14.6%) except for Schirmer's test. There was a significant difference in mean score of OSDI (p=0.004), TBUT (p=0.008) and cornea staining (p<0.001) between two groups. Primary angle closure glaucoma treated with more than two medications and for more than three years had worse ocular surface disease parameters but without statistical significant difference.
CONCLUSION: Ocular surface disease is common in PACG patients treated with topical pressure-lowering drugs. Topical pressure-lowering drugs caused significant OSD symptoms and signs except for tear production in PACG patients. Thorough evaluation of ocular surface disease is important to ensure appropriate treatment and intervention in PACG patients.

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