Browsing by Author "Kippie, Yunus"

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    Effects of xhosa specific solute carrier family 22-member 2 haplotypes on the cellular uptake of metformin and cimetidine
    (Elsevier B.V., 2025) Abrahams-October, Zainonesa; Kippie, Yunus; Pearce, Keenau; Benjeddou, Mongi
    Background: Studies have shown that solute carrier transporters play an important role in the transport and distribution of metformin, and that genetic variation(s) in solute carrier genes have play a role in the variation of metformin efficacy and disposition observed in populations. This study aimed to determine the cellular uptake efficiency of metformin in SLC22A2 coding haplotypes of an indigenous South African population. Methods and results: To determine metformin and cimetidine cellular uptake in transfected HEK-293 cells, ultra high-performance liquid chromatography was used to quantitate substrate concentration(s). Haplotypes 3 and 4 showed decreased metformin uptake, and haplotypes 2 and 5 displayed increased metformin uptake in comparison to haplotype 1 (i.e. wildtype haplotype). Haplotypes 2–5 showed decreased uptake of cimetidine in comparison to haplotype 1, implying a reduced sensitivity to the inhibition of cimetidine. In all haplotypes, no significant transport was observed for metformin and cimetidine. Passive permeability of metformin was favoured in haplotypes 3 and 5, whilst the remaining haplotypes demonstrate higher passive permeability ratios in favour of cimetidine. Conclusion: Haplotype 4, which is characterised by the non-synonymous single nucleotide polymorphisms rs316019 and rs8177517, demonstrates potential impaired metformin transport.
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    A post-market quality assessment of first-line, fixed-dose combination antiretrovirals in South Africa
    (Journal of Applied Pharmaceutical Science, 2019) Ward, Kim; Suleiman, Reem; Kippie, Yunus
    South Africa has the world’s largest antiretroviral (ARV) program and despite having stringent upstream medicine’s regulatory oversight, the post-market reassessment of ARV quality is prohibitively resource intensive. The aim of this study was to evaluate and compare the post-market quality of four fixed-dose combination (FDC) generics containing efavirenz (EFV) 600 mg, emtricitabine 200 mg, and tenofovir 300 mg against the innovator, Atripla® and according to the International Pharmacopoeia (IP). Generic tablet samples, sourced from a South African provincial depot, were subjected to the identification, content assay, dissolution, uniformity of weight and disintegration tests. An in-house reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated in lieu of the RP-HPLC IP method which proved to be unsuitable. All samples passed the identification, assay, uniformity of weight and disintegration tests and one generic FDC failed the dissolution test (at both stage 1 and 2), releasing 62.23% (standard deviation 20.43) of EFV in 30 minutes. One generic first-line ARV combination that is currently supplied to the South African public health sector was found to be substandard and this reinforces the need for routine ARV post-market surveillance, as well as reliable compendial methods to facilitate this undertaking.