Binding to human serum albumin of zidovudine (AZT) and novel AZT derivatives. Experimental and theoretical analyses☆

From Pediatric Covariate Model to Semiphysiological Function for Maturation: Part I–Extrapolation of a Covariate Model From Morphine to Zidovudine

“…The acid dissociation constant (pK a ) values for morphine are 7.9 and 9.6 17 and for zidovudine this value is around 9.7 18,19 and the octanol/water partition coefficient (log P) values for these compounds were reported to be around 0.75 17 and 0.05, 20,21 respectively. Plasma protein binding in adults ranges between 23 and 38% for both drugs, 20,22,23 and their hepatic extraction ratios in adults range between 0.5 and 0.65. [24][25][26] We cannot exclude that these similarities in drug characteristics have contributed to the good extrapolation potential of the pediatric covariate model for glucuronidation observed in this study, therefore, further studies on the applicability of the semiphysiological function for glucuronidation in children are required.…”

Fatty acid binding to serum albumin: Molecular simulation approaches

“…Details on an expected correlation between preferred binding sites and classes of bound ligands are well summarized in recent reviews [3,52,54]. Numerous experimental studies have also indicated that ligand-binding affinity to HSA can be modulated through simultaneous binding of FAs [55][56][57][58][59][60][61][62][63][64][65][66][67][68]. The modulation is caused by competitive binding between a ligand and an FA at the same binding site [17] or allosteric effects from the binding of FAs [62,[66][67][68].…”

“…The results of docking simulation are generally reported along with experimental studies such as equilibrium dialysis, circular dichroism, fluorometry, calorimetry, and spectroscopy [5,63,67,. In spite of this, choosing the correct target for docking can sometimes be difficult owing to the existence of multiple ligand-binding sites on HSA [3,17,54].…”

“…The HSA-ligand binding free energy (binding affinity) correlates with percentage plasma protein binding [143]. To date, calculated binding free energies have been reported for Gd-AAZTA complex (AAZTA = 6-amino-6-methylperhydro-1,4-diazepine tetraacetic acid) zidovudine and its derivatives [63], FAs (see section 3.2.2) [145], levamlodipine [76], flavones [78], perfluorooctanoic acid and perfluorooctane sulfonate [146], warfarin [147]. Fujiwara and Amisaki [147] have calculated binding free energies under various FA/HSA molar ratios, as described in section 3.2.…”

Development and Validation of a RP-HPLC Method for the Determination of Zidovudine and Its Related Substances in Sustained-release Tablets

“…A literature review revealed some analytical methods for the determination of AZT and its main metabolite in biological fluids. [1][2][3][4] However, there are few methods for the determination of AZT in pharmaceutical dosage forms. [5][6][7][8] Over the years, analytical validation methods have been redefined, and it can be argued that the concepts continue to evolve and are constantly under the responsibility of international organizations that establish procedures to enable the production of quality products, ensuring both efficacy and safety during handling and storage.…”