Comparative drug systemic exposure and clinical efficacy against resistant nematodes in lambs treated with different albendazole formulations.

A pharmaco-parasitological assessment of four different albendazole (ABZ) formulations was carried out in lambs infected with multiple resistant gastrointestinal (GI) nematodes. The comparative drug systemic exposure profiles (ABZ sulphoxide plasma concentrations) and anthelmintic efficacies (clinical endpoint measured through the faecal nematode eggs reduction counts) were determined for a reference formulation (RF) and three different test (T1, T2, T3) generic ABZ preparations. Fifty (50) Corriedale lambs naturally infected with multiple resistant GI nematodes were allocated into five experimental groups (n = 10). Animals in each group received treatment with either the RF, one of the test ABZ formulations (5 mg/kg by the intraruminal route) or were kept as untreated control. Blood samples were collected over 48 h post-treatment. ABZ parent drug was not recovered in the bloodstream. The ABZ sulphoxide (ABZSO) and sulphone (ABZSO(2) ) metabolites were measured in plasma by ultraviolet high-performance liquid chromatography over 36-48 h post-treatment. A faecal nematode egg count reduction test (FECRT) was performed at day 10th post-treatment to lambs from all treated and untreated groups, which indicated the predominance of nematodes with high level of resistance to ABZ. Both ABZSO C(max) and AUC(0-LOQ) values obtained for the RF (pioneer product) were significantly higher (P < 0.05) than those obtained for the T1 and T3 preparations. Based on the currently available bioequivalence criteria, the test (generic) ABZ formulations under evaluation could not be considered equivalent to the RF regarding the rate (C(max) ) and extent (AUC(0-LOD) ) of drug absorption (indirectly estimated through the ABZSO metabolite). A large variation in nematode egg counts did not permit to obtain statistically significant differences among formulations. However, a favourable trend in the efficacy against the most resistant nematodes was observed for the formulations with the highest ABZSO systemic exposure.

Variability in doses obtained from a multi-dose ophthalmic solution: a potential source of error in the assessment of compliance.

BACKGROUND: Assessment of compliance with prescribed therapy is an important aspect of patient management that can be overlooked. Compliance with topical ophthalmic medications is frequently assessed without knowledge of doses obtained per bottle. METHOD: Thirty-three normal subjects who agreed to participate were asked to instill one drop of Refresh Tears in each eye twice daily until a 3-ml bottle was empty. Each subject was also asked to record the date and time of each drop instillation using a calendar log sheet. On enrollment, the subjects were required to demonstrate proper drop instillation technique. With the use of the log sheets, doses obtained and administrations missed by each subject were tabulated. The 'expected count' per bottle was determined by counting the drops in Refresh Tears under laboratory conditions. RESULTS: Of the 26 subjects, who completed the study, the mean (SD) number of doses reportedly obtained was 63.7 +/- 17.1 (range = 26 to 110). The mean number of drops counted per bottle was 63.5 +/- 1.0 (range = 62 to 65). CONCLUSIONS: The range of doses reportedly obtained per bottle was quite large. This variability could represent a significant source of error if patient compliance is assessed by how long a bottle lasts.

Pigmented striae of the anterior lens capsule and age-associated pigment dispersion of variable degree in a group of older African-Americans: an age, race, and gender matched study.

PURPOSE: To investigate pigmented striae of the anterior lens capsule in African-Americans, a potential indicator of significant anterior segment pigment dispersion. METHODS: A group of 40 African-American subjects who exhibited pigmented lens striae (PLS) were identified from a non-referred, primary eye care population in Chicago, IL, USA. These subjects were then compared to an age, race, and gender matched control group relative to refractive error and the presence or absence of diabetes and hypertension. RESULTS: The PLS subjects (mean age = 65.4 +/- 8.8 years, range = 50-87 years) consisted of 36 females and 4 males. PLS were bilateral in 36 (85%) of the 40 subjects. Among the eyes with PLS, 21 (55%) of 38 right eyes and 22 (61%) of 36 left eyes also had significant corneal endothelial pigment dusting, commonly in the shape of a Krukenberg's spindle. Ten (25%) of the PLS subjects had either glaucoma or ocular hypertension (7 bilateral, 3 unilateral). The presence of trabecular meshwork pigment varied from minimal to heavy. The mean +/- SD (range) refractive error of the PLS right eyes was +1.61 +/- 1.43D (-1.50 to +5.00D) and +1.77 +/- 1.37D (-1.00 to +5.00D) for the left eyes. Based on these data, the PLS right eyes were +1.63D (Student's t, p = 0.0001; 95% CI = +0.82 to +2.44D) more hyperopic on average than the control right eyes, and the PLS left eyes were +1.77D (p = 0.0001; 95% CI = +0.92 to +2.63D) more hyperopic on average than the control left eyes. Trend analysis showed a gradually increasing likelihood of PLS with increasing magnitude of hyperopia in both eyes (Mantel-Haenszel chi-square, p = 0.001). Among PLS subjects, 24 (60%) of 40 were hypertensive and 9 (23%) of 40 were diabetic. However, these proportions were not significantly different (two-tailed Fisher's exact test; hypertension: p = 0.30; diabetes: p = 0.70) from the randomly selected controls. CONCLUSIONS: Among our African-American group, which consisted predominately of females >50 years of age, the likelihood of PLS increased with increasing hyperopic refractive error. This finding is consistent with the possibility that PLS may, in some circumstances, indicate a significant pigment dispersal process due to iris-lens rubbing that may be associated with crowding of anterior segment structures. Additional study is warranted to further assess the nature of PLS, their precise relationship with an age-related pigment dispersal process, and their true significance as a risk factor for development of glaucoma.

The incidence and economic significance of ovine toxoplasmosis in Uruguay.

Antibodies to Toxoplasma gondii were measured before and after pregnancy in a 1:64 dilution of sera with the direct agglutination test in 1613 ewes from 18 farms in eight different counties of Uruguay from 1992 to 1994. The overall seroprevalence increased from 28.7% before mating to 38.5% after lambing in 2.5 years and thus the incidence was 9.8%. Losses due to toxoplasmosis during pregnancy were estimated to be 1.4-3.9% of the total number of ewes investigated, amounting to approximately US$1.4-4.7 million for the whole country.

The incidence and economic significance of ovine toxoplasmosis in Uruguay.

Antibodies to Toxoplasma gondii were measured before and after pregnancy in a 1:64 dilution of sera with the direct agglutination test in 1613 ewes from 18 farms in 8 different counties of Uruguay from 1992 to 1994. The overall seroprevalence increased from 28.7% before mating to 38.5% after lambing in 2.5 yr and thus, the incidence was 9.8%. Losses due to toxoplasmosis during pregnancy were estimated to be 1.4 to 3.9% of the total number of ewes investigated, amounting to approximately US$1.4-4.7 million for the whole country.