Browsing by Author "Phogole, Cassius"

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    An analytical investigation of the impact of crushing of first-line antituberculosis medication and administration via a nasogastric tube
    (Stellenbosch : Stellenbosch University, 2022-11) Phogole, Cassius; Kellermann, Tracy; Faculty of Medicine and Health Sciences. Dept. of Medicine. Division of Clinical Pharmacology.
    ENGLISH ABSTRACT: Background Currently, the treatment of TB patients admitted to an intensive care unit (ICU) in South African Hospitals is performed by the off-label practice of crushing the first-line antituberculosis drugs isoniazid (INH), rifampicin (RIF), pyrazinamide (PZA) and ethambutol (EMB) and administration to the patients through a nasogastric (NG) tube as the majority of these patients are often sedated or intubated and therefore cannot swallow the whole tablets. This has, however, been associated with low drug exposure insufficient to effectively treat the Mycobacterial infection. Additionally, there is a paucity of alternative intravenous (IV) formulations of first-line antituberculosis drugs, especially in developing countries. The stability and solubility of these crushed drugs dissolved in water are questionable. Furthermore, the impact of the removal of the protective outer tablet coating and its effect on absorption and subsequent bioavailability has not been elucidated in the literature. Moreover, drug loss of crushed first-line antituberculosis drugs by adsorption to the surface materials used during medication preparation and administration via NG tube has also not been documented. Therefore, the present study aimed to investigate the root cause of the poor plasma drug exposure observed when crushing the first-line antituberculosis drugs and administration through an NG tube using laboratory-based techniques with possible translational interventions that can be applied in clinical settings to ameliorate their bioavailability. Methods The aqueous solubility of crushed drugs under the inversion mixing method was evaluated against easily implementable mixing methods (sonication and vortexing) with/without ascorbic acid (Asc). Moreover, the aqueous stability assessment of these crushed first-line antituberculosis drugs in mono-suspensions with/without Asc and co-suspensions at room and low temperatures was executed as well. The stability of the whole/crushed tablets in fasted-state simulated gastrointestinal fluids (FSSGIFs) was evaluated with/without Asc. Lastly, the drug loss by adsorption to the surface materials used during medication preparation and in vitro administration through an NG tube was quantitatively determined. Results Rifampicin (RIF) was the only drug showing poor aqueous solubility and instability in the simulated-gastric fluid. However, the addition of Asc has been shown to significantly (P<0.001) improve RIF solubility in both water and FSSGIFs with no detrimental effects. A minimum recommended volume of water (10 ml) to rinse the NG tube after administration of medication was shown to be inadequate to clear off all the residues of crushed antituberculosis medication. However, when an additional rinsing step with another 10 mL of water (total volume of 20 mL) was employed in the current study the amount of APIs of crushed first-line antituberculosis drugs adsorbed to these surface materials was significantly (p<0.001) reduced. Conclusion Co-administration of first-line antituberculosis medication with Asc when off-label crushing practice is used may improve RIF bioavailability. Furthermore, rinsing the NG tube with 20 mL of water after administering TB medication was shown to ensure adequate drug delivery, which may improve the bioavailability of nonpolar drugs that adhere to the surface of an NG tube.