Samar F. Farid

Management of intraepithelial and invasive neoplasia of the cornea and conjunctiva: a long-term follow up.

Purpose: The aim of this work is to report the long-term results of using immunotherapy for the management of cornea and conjunctiva intraepithelial neoplasia and squamous cell carcinoma after surgical excision of the neoplasm. Methods: Ten eyes of 10 patients with cornea and conjunctiva intraepithelial neoplasia or squamous cell carcinoma had wide surgical excisions of the neoplasm after evaluation of the level of corneal involvement using ultrasound biomicroscopy. All eyes received topical cyclosporine A (0.05%) and topical mitomycin C (0.01%) 4 times daily for 12 weeks after surgery. All eyes were followed up every month for 6 months and then every 6 months for another 18 months. Results: All eyes showed total cure with no recurrence during the 2-year follow-up period. Epithelial toxicity (punctate keratopathy) occurred in 3 eyes, ocular irritation and mild conjunctival hyperemia in 5 eyes, and lid toxicity in 2 cases during the treatment with mitomycin C. There were no serious complications that necessitated stopping the treatment. Conclusion: During a 2-year follow-up period, the use of topical cyclosporine A (0.05%) combined with mitomycin C (0.01%) as an adjunctive treatment after surgical excision in cornea and conjunctiva intraepithelial neoplasia and squamous cell carcinoma was found to prevent tumor recurrence, especially in extensive lesions, when surgical excision cannot ensure a tumor-free margin.

Subconjunctival bevacizumab for corneal neovascularization

Acta Ophthalmol. 2010: 88: 868–871

Relative bioavailability of griseofulvin lyophilized dry emulsion tablet vs. immediate release tablet: A single-dose, randomized, open-label, six-period, crossover study in healthy adult volunteers in the fasted and fed states

The oral bioavailability of griseofulvin (GF) formulated as a fast disintegrating lyophilized dry emulsion (LDE) tablet was studied and compared to the commercially available immediate release (IR) tablet, as a reference, in both the fasted and fed states in nine healthy volunteers after a single oral dose (125 mg) in a crossover design. Furthermore the LDE tablets were ingested with and without water under both the fasted and fed states. In the fasted state, the rate of absorption was found to be significantly faster from LDE tablets, in the presence and absence of water, as shown by a higher C(max) (more than two times higher, p=0.0001) and a shorter t(max) (by more than 3h, p=0.0001) compared to IR tablets. The extent of absorption, expressed as AUC, from LDE tablets in the presence and absence of water was 65% and 77% larger and statistically significantly different relative to the mean AUC from IR tablets (p=0.006). In the fed state, C(max) from LDE tablets ingested with and without water was found to be about 30% and 50% higher, respectively, than the immediate release tablets. A shorter t(max) was also shown whether LDE tablets were ingested with or without water in the fed state as compared to immediate release tablets. The mean AUC from LDE tablets under fed conditions in the presence of water was about 21% larger and was not statistically significantly different from AUC from immediate release tablets (p=0.517). When ingested without water, AUC from LDE tablets was about 43% larger and statistically significantly different relative to AUC from IR tablets (p=0.033). The mean AUC from the LDE tablet ingested with water under fed conditions relative to AUC from LDE tablet ingested without water was not statistically significantly different (p=0.454). Results show that the food effect of the high fat meal is very pronounced in case of the immediate release tablets, Fulvin, than in case of LDE tablets whether given with or without water.

Development and validation of LC-MS/MS assay for the determination of the prodrug Midodrine and its active metabolite Desglymidodrine in plasma of ascitic patients: Application to individualized therapy and comparative pharmacokinetics.

Midodrine (MD) is a prodrug that is converted after oral administration to Desglymidodrine (DMD). In this study, an LC-MS/MS assay was developed and validated for investigation of the pharmacokinetics of MD and DMD in non azotemic patients with liver cirrhosis and tense ascites. Results were compared to those noted with healthy volunteers following the adminstration of a single oral dose of MD. Sample preparation was performed by liquid-liquid extraction using t-butyl methyl ether. HPLC separation was carried out using RP C18 column (4.6mm×50mm, 5μm). Isocratic elution was performed using methanol:0.2% formic acid (70:30, v/v) as the mobile phase, at a flow rate of 0.7mL/min. Tandem mass spectrometric detection was employed at positive electrospray ionization in MRM mode for the determination of MD and DMD. Analysis was carried out within 1.0min over a concentration range of 0.50-40.00ng/mL for the prodrug and its active metabolite. The assay was validated according to FDA guidelines for bioanalytical method validation and satisfactory results were obtained. The applicability of the assay for the determination of the pharmacokinetic parameters of MD and DMD and personalized therapy was demonstrated in healthy volunteers and ascitic patients. Results revealed significant differences in pharmacokinetic parameters among the studied groups. Such differences were explained on the basis of the medical condition and co-adminstered medications exerting possible drug-drug interaction. Results confirmed the need for implementation of reliable analysis tools for therapeutic dose adjustment.

Hepatoprotective Efficacy of Ursodeoxycholic Acid in Pediatrics Acute Lymphoblastic Leukemia

Ursodeoxycholic acid (UDCA) possesses a hepatoprotective effect in drug-induced hepatotoxicity. In a prospective randomized parallel study, 39 children with acute lymphoblastic leukemia (ALL) were randomized to receive UDCA with chemotherapy for 6 months, then discontinued UDCA and were followed up for 3 months, (UDCA group) (N = 19) or receive chemotherapy without UDCA and followed up for 9 months (control group) (N = 20). In this pilot study, UDCA treatment was associated with a trend toward decreased levels of hepatic transaminases when concomitantly administered with chemotherapy and, therefore, safer outcome in children with ALL. Future studies with a larger sample size are needed to confirm the efficacy and safety of UDCA in this setting.

Randomized comparative efficacy and safety study of intermittent simvastatin versus fenofibrate in hemodialysis

AIM Compare the safety and efficacy of intermittent fenofibrate versus simvastatin in chronic hemodialysis patients. PATIENTS & METHODS Sixty patients received either fenofibrate 100 mg or simvastatin 20 mg after their dialysis session (parallel study). The safety and efficacy of drugs on lipid profile, oxidized low-density lipoprotein (Ox-LDL), glutathione peroxidase and C-reactive protein were compared before and after 16-week treatment. RESULTS After treatment, significant increase in glutathione peroxidase, significant decrease in total cholesterol, triglycerides, low density lipoprotein (LDL) and ox-LDL (p < 0.05) and no significant changes in C-reactive protein (p > 0.05) were observed in both groups. Both drugs were well tolerated with no serious side effects reported by the patients. CONCLUSION Both drugs have comparable efficacy and safety when used as intermittent low dose regimen in hemodialysis. Larger studies with longer follow-up periods are needed to confirm our new findings.