Comparative bioavailability of some locally manufactured betamethasone valerate containing preparations

The bioavailabilities of three locally manufactured proprietary betamethasone- 17-valerate containing creams and ointments were compared by measuring their abilities to cause blanching of human skin after topical application. The preparations studied were Betnovate Cream and Ointment, Celestoderm-V Cream and Ointment and Persivate Cream and Ointment. Celestoderm-V cream displayed a significantly superior blanching activity over both Betnovate and Persivate creams in' the occluded mode, whereas Persivate cream displayed a significantly superior blanching activity over both Betnovate and Celestoderm-V creams in the unoccluded mode. Persivate ointment was found to produce a significantly superior blanching activity over Betnovate and Celestoderm-V ointments in both the occluded and unoccluded modes of application

A stability-indicating HPLC assay with on-line clean-up for betamethasone 17-valerate in topical dosage forms

A stability-indicating high-performance liquid chromatographic method with on-line clean-up has been developed for the analysis of betamethasone 17-valerate in topical dosage forms. A short pre-column containing 10 μm octadecylsilane mounted into the sample loop position of an injection valve was used as the primary clean-up step. The utilization of a diode-array UV detector allowed the quantitative analysis of betamethasone 17-valerate together with its degradation product, betamethasone 21-valerate, as well as the qualitative analysis of these compounds, relevant internal standards and the preservatives chlorocresol and methyl hydroxybenzoate contained in the cream and lotion formulations, respectively. Typically, cream and lotion dosage forms were dissolved in acetonitrile and ointments in tetrahydrofuran, internal standards added and aliquots injected onto the analytical system. Dosage form excipients were retained on the loop column and back-flushed to waste with the aid of a second solvent pump while components of interest were allowed to transfer to the analytical column for quantitative analysis. The method is accurate, precise and stability indicating and permits the rapid on-line analysis of betamethasone 17-valerate from complex topical formulation matrices without prior extractions

Potency ranking of two new topical corticosteroid creams containing 0.1% desonide or 0.05% halometasone utilizing the human skin-blanching assay

The human blanching assay was used to assess the potency of two new proprietary corticosteroid creams. The blanching abilities of 0.1% desonide cream and 0.05% halometasone cream were evaluated relative to the blanching elicited by 0.05% clobetasol 17-propionate cream, 0.1% betamethasone 17-valerate cream and 0.05% clobetasone 17-butyrate cream. The results of the trial indicated that the 0.1% desonide cream falls into the potent group of topical corticosteroid preparations and the 0.05% halomethasone cream falls into the moderately potent group

The human skin-blanching assay for in vitro topical corticosteroid assessment. I. Reproducibility of the assay

The human skin blanching (vasoconstriction) assay for the assessment of topical corticosteroids has been in use for over 30 years, the intensity of the drug-induced blanching being assessed subjectively by eye. Both arms of several male and female volunteers are used for product application and more than one observer is used to estimate the degree of induced blanching. There are, therefore, numerous variables which are inherent in the assay procedure. This investigation consisted of three identical trials performed at 8-week intervals, utilising the same 18 volunteers and the same three observers in an attempt to address the question of reproducibility of the assay. From the results obtained it is clear that the assay methodology is capable of consistently distinguishing, on a rank order basis, between preparations which show similar blanching (chemically-equivalent formulations). The similarity of the results for the three individual trials gives considerable confidence to results produced using this methodology. An experiment designed to test the reproducibility of the blanching scores showed that the observers are capable of producing identical results even though visual observation is highly subjective

The human skin blanching assay for in vivo topical corticosteroid assessment. II. Subject- and observer-dependent variation in blanching responses

The human skin blanching (vasoconstriction) assay for the assessment of topical corticosteroids has been in use for over 30 years, the intensity of the drug-induced blanching being assessed subjectively by eye. Both arms of several male and female volunteers are used for product application and more than one observer is used to estimate the degree of induced blanching. There are, therefore, numerous variables which are inherent in the assay procedure. This investigation consisted of three identical trials performed at 8-week intervals, utilising the same 18 volunteers and the same three observers in an attempt to address the question of reproducibility of the assay. From the results obtained it is clear that the assay methodology is capable of consistently distinguishing, on a rank order basis, between preparations which show similar blanching (chemically-equivalent formulations). The similarity of the results for the three individual trials gives considerable confidence to results produced using this methodology. An experiment designed to test the reproducibility of the blanching scores showed that the observers are capable of producing identical results even though visual observation is highly subjective

Effect of African Potato (Hypoxis Hemerocallidea) on the Pharmacokinetics of Efavirenz

Purpose. The purpose of this study was to evaluate the effect of the African potato (AP) on the pharmacokinetics of efavirenz. Methods. A single-dose, two-phase sequential study was conducted over 31 days in 10 healthy volunteers. On day 1 of the study, volunteers were administered a 600 mg efavirenz tablet, and blood samples were collected before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 18, 24, 36 and 48 hours after dosing. From day 16, a traditionally prepared AP decoction was administered daily until day 30. On day 29, volunteers were administered a single 600 mg dose of efavirenz, as was done on day 1. Plasma samples were harvested immediately after blood sample collection and frozen at –80ºC until assayed. Plasma concentrations of efavirenz were determined by a validated high performance liquid chromatography (HPLC) method with UV detection, and pharmacokinetic parameters were calculated. Geometric mean ratios of Cmax and AUC0-48 of efavirenz before and after co-administration of 14 successive daily doses of AP were compared. Results. All subjects completed the study. The geometric mean ratios of Cmax and AUC0-48 were 97.30 and 102.82 with corresponding 90% confidence intervals (CIs) of 78.81 - 120.14 and 89.04 - 118.80, respectively. Conclusion. Pharmacokinetic data generated during this study indicated that AP did not significantly alter the pharmacokinetics of efavirenz. Hence, co-administration of AP is unlikely to affect the clinical usage of efavirenz. South African Medical Journal Vol. 98 (12) 2008: pp. 945-94

Breeding value estimation for somatic cell score in South African dairy cattle

Two fixed regression testday models were applied for variance component estimation and prediction of breeding values for somatic cell score, using testday records of the first three lactations of South African Holstein and Jersey cows. The first model (ML-model) considered the testdays of the different lactations as different traits in a multiple-trait animal model and the second analysis (RM-model) treated later lactation records as repeated measures of the first lactation. Heritabilities from the RM-model were more in the range of literature estimates compared to that of the ML-model, i.e. 0.19 + 0.003 for the Holstein breed and 0.18 + 0.003 for the Jersey breed. Rank correlations indicated that minor changes occur in the ranking of proven sires between breeding values obtained from the ML- and RM-models. Although genetic correlations between parities are not unity, the RM-model estimates more competitive variances and requires extensively less computer time to predict breeding values compared to the ML-model and are therefore recommended for breeding value estimation on a national basis. South African Journal of Animal Science Supp 2 2004: 32-3

Test-day models for South African dairy cattle for participation in international evaluations

Variance components and breeding values of production traits and somatic cell score of South African Guernsey, Ayrshire, Holstein and Jersey breeds have been estimated using a multi-lactation repeatability test-day model, including tests of the first three lactations as repeated measures and fitting the permanent environmental effect across lactations. Multitrait evaluations were done for the production traits (milk, butterfat and protein) and single trait evaluations for somatic cell score. Heritability estimates were comparable with yield and somatic cell score estimates obtained by test-day models from other countries (17-24% for milk yield; 10-13% for butterfat yield; 14-19% for protein yield and 6-8% for somatic cell score). Proofs of qualifying sires were sent to the International Bull Evaluation Service (INTERBULL) for participation in the March 2005 test runs. Genetic correlations between South Africa and other participating countries, estimated by INTERBULL, compared well with those amongst the other participating countries. Trend validation tests were successful using this methodology for all traits and breeds except for somatic cell score of the Guernsey breed, due to insufficient data for this trait. South Africa can now participate in routine INTERBULL evaluations to obtain Multiple Across Country Evaluation (MACE) breeding values, using this methodology. South African Journal of Animal Science Vol. 36(1) 2006: 58-7

Comparison of breeding values and genetic trends for production traits estimated by a Lactation Model and a Fixed Regression Test-day Model

A comparison of breeding values and genetic trends of production traits from two models is made. One set of breeding values and trends was estimated by the September/October 2003 South African National Genetic Evaluation, using a Lactation Model (LM). The other set was obtained in the 2004 South African National Genetic Evaluation, using a Fixed Regression Test-day Model (TDM). This comparison is made for Ayrshire, Guernsey, Holstein and Jersey cows participating in the South African Dairy Animal Improvement Scheme. Specific differences between the two models were documented, with differences in statistical methodology and inclusion of test-day records of the first three parities in the TDM vs. only first lactation 305-day yields in the LM, as the main differences. Significant reranking of especially cows and unproven sires occurred between the models. Genetic trends of the TDM were not as steep as those from the LM, as the trait that was selected was first lactation yield, while the TDM trends reflect genetic progress over the first three parities. South African Journal of Animal Science Vol. 36(2) 2006: 71-7

Adjustment of heterogenous variances and a calving year effect in test-day models for national genetic evaluation of dairy cattle in South Africa

South Africa implemented test-day models for genetic evaluations of production traits, using a Fixed Regression Test-Day Model (FRTDM), which assumes equal variances of the response variable at different days in milk, the explanatory variable. Data at the beginning and at the end of lactation period, have higher variances than tests in the middle of the lactation. Furthermore, first lactations have lower mean and variances compared to second and third lactations. This is a deviation from the basic assumptions required for the application of repeatability models. A modification was therefore implemented to reduce the effect of deviating from this assumption. Test-day milk, butterfat and protein yield records of Jersey cows, participating in the South African Milk Recording Scheme, were therefore pre-adjusted such that the variances are on the same scale. Variance components estimated using the adjusted records were higher than using unadjusted records. Convergence of breeding value estimation is reached significantly faster when using adjusted data (± 4000 iterations) compared to unadjusted records (± 15 000 iterations). Although cow and bull rankings were not influenced much, significant changes in breeding values for individual animals and genetic trends of especially young animals, were found. South African Journal of Animal Science Vol. 36(3) 2006: 165-17