Archives: Projects/Publication

Short-term efficacy and safety of intravitreal ranibizumab for myopic choroidal neovascularization.

Short-term efficacy and safety of intravitreal ranibizumab for myopic choroidal neovascularization.

Short-term efficacy and safety of intravitreal ranibizumab for myopic choroidal neovascularization.

Silva, R., Ruiz-Moreno, J., Nascimento, J., Carneiro, A., Rosa, P., Barbosa, A., Carvalheira, F., Faria de Abreu, J., Cunha-Vaz, J.

Retina, 2008 Oct; 28(8): 117-23.

2008

Laboratory diagnosis of endophthalmitis: comparison of microbiology and molecular methods in the European Society of Cataract & Refractive Surgeons multicenter study and susceptibility testing.

Laboratory diagnosis of endophthalmitis: comparison of microbiology and molecular methods in the European Society of Cataract & Refractive Surgeons multicenter study and susceptibility testing.

Laboratory diagnosis of endophthalmitis: comparison of microbiology and molecular methods in the European Society of Cataract & Refractive Surgeons multicenter study and susceptibility testing.

Seal, D., Reischl, U., Behr, A., Ferrer, C., Alió, J., Koerner, RJ., Barry, P.,; ESCRS Endophthalmitis Study Group

J. Cataract Refract Surg. 2008 Sep; 34(9):1439-50.

2008

Evidence of widespread retinal dysfunction in patients with stargardt disease and morphologically unaffected carrier relatives.

Evidence of widespread retinal dysfunction in patients with stargardt disease and morphologically unaffected carrier relatives.

Evidence of widespread retinal dysfunction in patients with stargardt disease and morphologically unaffected carrier relatives.

Maia-Lopes, S., Silva, E.D., Silva, M.F., Reis, A., Faria, P., Castelo-Branco, M.

Invest. Ophthalmol. Vis. Sci. 2008 Mar; 49(3):1191-9.

2008

Effect of nebicapone on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.

Effect of nebicapone on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.

Effect of nebicapone on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects.

Luis Almeida, Amílcar Falcão, Manuel Vaz-da-Silva, Teresa Nunes, Ana-Teresa Santos, José-Francisco Rocha, Carla Neta, Tice Macedo, C. Fontes-Ribeiro, P. Soares-da-Silva

Abstract

Objective  Nebicapone is a new catechol-O-methyltransferase inhibitor. In vitro, nebicapone has showed an inhibitory effect upon CYP2C9, which is responsible for the metabolism of S-warfarin. The objective of this study was to investigate the effect of nebicapone on warfarin pharmacokinetics and pharmacodynamics in healthy subjects.

Methods  Single-centre, open-label, randomised, two-period crossover study in 16 healthy volunteers. In one period, subjects received nebicapone 200 mg thrice daily for 9 days and a racemic warfarin 25-mg single dose concomitantly with the nebicapone morning dose on day 4 (test). In the other period, subjects received a racemic warfarin 25-mg single dose alone (reference). The treatment periods were separated by a washout of 14 days.

Results  For R-warfarin, mean ± SD Cmax was 1,619 ± 284 ng/mL for test and 1,649 ± 357 ng/mL for reference, while AUC0-t was 92,796 ± 18,976 ng·h/mL (test) and 73,597 ± 11,363 ng·h/mL (reference). The R-warfarin test-to-reference geometric mean ratio (GMR) and 90% confidence interval (90%CI) were 0.973 (0.878–1.077) for Cmax and 1.247 (1.170–1.327) for AUC0-t . For S-warfarin, mean ± SD Cmax was 1,644 ± 331 ng/mL for test and 1,739 ± 392 ng/mL for reference, while AUC0-t was 66,627 ± 41,199 ng·h/mL (test) and 70,178 ± 42,560 ng·h/mL (reference). The S-warfarin test-to-reference GMR and 90%CI were 0.932 (0.845–1.028) for Cmax and 0.914 (0.875–0.954) for AUC0-t . No differences were found for the pharmacodynamic parameter (INR).

Conclusion  Nebicapone showed no significant effect on S-warfarin pharmacokinetics or on the coagulation endpoint (INR). A mild inhibition of the R-warfarin metabolism was found but is unlikely to be of clinical relevance.

European Journal of Clinical Pharmacology, 2008 Oct; 64 (10): 961-966.

2008
http://www.springerlink.com/content/m3617087h1347604/?p=cbf93c588e5a491e9c51cd20dc82f48d&pi=0

Dosage form proportionality and food-effect of the final tablet formulation of eslicarbazepine acetate in healthy volunteers

Dosage form proportionality and food-effect of the final tablet formulation of eslicarbazepine acetate in healthy volunteers

Dosage form proportionality and food-effect of the final tablet formulation of eslicarbazepine acetate in healthy volunteers

Carlos Fontes-Ribeiro, Tice Macedo, Teresa Nunes, Carla Neta, Teófilo Vasconcelos, Rui Cerdeira, Ricardo Lima, José-Francisco Rocha, Amílcar Falcão, Luís Almeida, Patrício Soares-da-Silva

Abstract:
Objective: To investigate the dosage form proportionality and food effect of the final tablet formulation of eslicarbazepine acetate (ESL) in healthy volunteers.

Methods: This was a randomized, three-way crossover, single-centre study in 18 healthy volunteers. Subjects received a single dose of oral ESL 800 mg following a standard meal in one period, and following 10 hours of fasting in two separate periods (in the form of one 800 mg tablet [reference] or two 400 mg tablets [test]). The statistical method was based upon the 90% confidence interval (CI) of maximum observed plasma drug concentration (Cmax), area under the plasma concentration time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the lower limit of quantification (AUCt) and AUC from time zero to infinity (AUC[infinity]) geometric means ratios (GMRs) of BIA 2-005, the enantiomeric mixture of the ESL active metabolite eslicarbazepine and its enantiomer R-licarbazepine. Bioequivalence was assumed when the 90% CI of the test/reference GMR fell within the bioequivalence acceptance interval (80.00, 125.00).

Results: Following a single dose of ESL 800 mg in the forms of two 400 mg tablets and one 800 mg tablet, the test/reference GMR (%) and 90% CI for Cmax, AUCt and AUC[infinity] were 100.78% (93.91, 108.16), 100.37% (97.82, 102.99) and 100.48% (97.91, 103.13), respectively. Following administration of one 800 mg tablet in fed (test) and fasting (reference) conditions, the test/reference GMR and 90% CI for Cmax, AUCt and AUC[infinity] were 100.96% (94.08, 108.35), 96.79% (94.34, 99.32) and 96.75% (94.27, 99.29), respectively. Treatments were well tolerated.

Conclusions: The bioequivalence criteria between the ESL 400 mg and 800 mg tablets were met and dosage form proportionality was demonstrated. The presence of food had no influence on ESL pharmacokinetics, indicating that ESL can be administered without regard to meals with no significant effects on drug disposition or extent of systemic exposure.

 

 

Drugs in R&D 2008; 9 (6): 447-454.

2008

Increased-Resolution OCT Thickness Mapping of the Human Macula: A Statistically Based Registration.

Increased-Resolution OCT Thickness Mapping of the Human Macula: A Statistically Based Registration.

Increased-Resolution OCT Thickness Mapping of the Human Macula: A Statistically Based Registration.

Bernardes R., Santos T., Cunha-Vaz J.

Purpose: To describe the development of a technique that enhances spatial resolution of retinal thickness maps of the Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA). A retinal thickness atlas (RT-atlas) template was calculated, and a macular coordinate system was established, to pursue this objective.

Methods: The RT-atlas was developed from principal component analysis of retinal thickness analyzer (RTA) maps acquired from healthy volunteers. The Stratus OCT radial thickness measurements were registered on the RT-atlas, from which an improved macular thickness map was calculated. Thereafter, Stratus OCT circular scans were registered on the previously calculated map to enhance spatial resolution.

Results: The developed technique was applied to Stratus OCT thickness data from healthy volunteers and from patients with diabetic retinopathy (DR) or age-related macular degeneration (AMD). Results showed that for normal, or close to normal, macular thickness maps from healthy volunteers and patients with DR, this technique can be an important aid in determining retinal thickness. Efforts are under way to improve the registration of retinal thickness data in patients with AMD.

Conclusions. The developed technique enhances the evaluation of data acquired by the Stratus OCT, helping the detection of early retinal thickness abnormalities. Moreover, a normative database of retinal thickness measurements gained from this technique, as referenced to the macular coordinate system, can be created without errors induced by missed fixation and eye tilt.

Invest. Ophthalmol. Vis. Sci; 2008; 49 (5): 2046-2052.

2008
http://www.iovs.org/cgi/reprint/49/5/2046

Method and apparatus for measuring quantity of a fluorochrome in a biological environment.

Method and apparatus for measuring quantity of a fluorochrome in a biological environment.

Method and apparatus for measuring quantity of a fluorochrome in a biological environment.

Schwartz A., Bernardes R., Franke S., Morgado A.

World Intellectual Property Organization. WO 2008/067525 A2, 5 de Julho de 2008.

2008