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Virendra Rambiritch,1 Poobalan Naidoo,2 Breminand Maharaj,1 Goonaseelan Pillai3 1University of KwaZulu-Natal, Durban, 2Department of Internal Medicine, RK Khan Regional Hospital, Chatsworth, South Africa; 3Novartis Pharma AG, Basel, Switzerland Aim: The aim of this study was to describe the pharmacokinetics (PK) of glibenclamide in poorly controlled South African type 2 diabetic subjects using noncompartmental and model-based methods. Methods: A total of 24 subjects with type 2 diabetes were administered increasing doses (0 mg/d, 2.5 mg/d, 5 mg/d, 10 mg/d, and 20 mg/d) of glibenclamide daily at 2-week intervals. Plasma glibenclamide, glucose, and insulin determinations were performed. Blood sampling times were 0 minute, 30 minutes, 60 minutes, 90 minutes, and 120 minutes (post breakfast sampling) and 240 minutes, 270 minutes, 300 minutes, 330 minutes, 360 minutes, and 420 minutes (post lunch sampling) on days 14, 28, 42, 56, and 70 for doses of 0 mg, 2.5 mg, 5.0 mg, 10 mg, and 20 mg, respectively. Blood sampling was performed after the steady state was reached. A total of 24 individuals in the data set contributed to a total of 841 observation records. The PK was analyzed using noncompartmental analysis methods, which were implemented in WinNonLin®, and population PK analysis using NONMEM®. Glibenclamide concentration data were log transformed prior to fitting. Results: A two-compartmental disposition model was selected after evaluating one-, two-, and three-compartmental models to describe the time course of glibenclamide plasma concentration data. The one-compartment model adequately described the data; however, the two-compartment model provided a better fit. The three-compartment model failed to achieve successful convergence. A more complex model, to account for enterohepatic recirculation that was observed in the data, was unsuccessful. Conclusion: In South African diabetic subjects, glibenclamide demonstrates linear PK and was best described by a two-compartmental model. Except for the absorption rate constant, the other PK parameters reported in this study are comparable to those reported in the scientific literature. The study is limited by the small study sample size and inclusion of poorly controlled type 2 diabetic subjects. Keywords: type 2 diabetes mellitus, glibenclamide, pharmacokinetics, compartmental, NONMEM model

This paper questions whether the second Millennium Development Goal of achieving universal primary education targets by 2015 for all children to complete a full course of primary schooling, can be realised. A key contention of this paper is that this forecast is far-fetched when we take into cognizance refugee children's accessibility to education. As much as it has reported that enrolment in primary education is on the rise, refugee access to education remains a great challenge. The purpose of this paper is to explore refugee children's access to education, with reference to the South African experience. The study adopted a qualitative approach and case study design. Refugee children have limited opportunities to secondary education and experience many problems accessing primary education because of their refugee status. The study found that there are two forms of barriers to refugee children's access to education: obstacles to enrolling in a school and barriers in respect of sustaining themselves after enrolling at schools. It is concluded that the refugee children's lack of access to education does not support the attainment of second Millennium Development Goal. The study recommends enlightening school management teams about refugee children's rights to quality education. This South African study, which is symptomatic of the global refugee experience, suggests the Second Millennium Development Goal will not be realised unless the education of refugee children is taken seriously.

Virendra Rambiritch,1 Breminand Maharaj,2 Poobalan Naidoo3 1Biomedical Research Ethics Committee, University of Kwazulu-Natal, Durban, KwaZulu-Natal, South Africa; 2Department of Therapeutics and Medicines Management, University of Kwazulu-Natal, Durban, KwaZulu-Natal, South Africa; 3Boehringer-Ingelheim, Medical Affairs, Johannesburg, Gauteng, South Africa Background: The purpose of this study was to investigate the effect of glibenclamide dose escalation on blood glucose and insulin in patients with poorly controlled type 2 diabetes. Methods: Twenty-two subjects with type 2 diabetes were administered increasing doses (0, 2.5, 5, 10, and 20 mg/day) of glibenclamide at 2-week intervals. Glibenclamide, glucose, and insulin determinations were performed. Results: The decrease in mean blood glucose from zero dose was 20%, 22%, 26%, and 28% for doses of 2.5, 5, 10, and 20 mg/day, respectively, which was significant from zero dose to 2.5 mg/day (P≤0.001). There were no significant decreases in glucose concentration beyond 2.5 mg/day. The percentage increase in mean insulin from zero dose was 51%, 58%, 44%, and 33% for 2.5, 5, 10, and 20 mg/day respectively. Mean blood insulin increased significantly from zero dose to 2.5 mg/day (P≤0.001). There were no significant increases in mean insulin concentration beyond 2.5 mg/day. Conclusion: The results of this study suggest that increasing doses of glibenclamide do not produce a proportional increase in insulin secretion or a proportional decrease in blood glucose concentration. Keywords: type 2 diabetes, glibenclamide, dose-escalation, insulin, glucose

The effect of the industrial solvent n-hexane on liver function was investigated by studying the livers of rats injected subcutaneously with 0.1 ml n-hexane for seven consecutive days. The results showed that n-hexane causes fatty changes in liver. As compared to the control group, rats injected with the solvent had lower perfusate glucose concentrations. Perfusate lactate levels and lactate:pyruvate ratios were greater.