Solubility renal clearance

Once absorbed, the drug needs to stay in solution as it equilibrates with all the body compartments. For extensively renally cleared drugs, precipitation or crystallization in the kidneys is a particular concern, as it leads to crystalluria [6, 7]. Changes in pH and salt concentrations in the kidneys, the therapeutic dose required, and the rate of renal clearance will affect the risk of crystalluria. Computational models predicting solubility at differing pH values may be useful in the context of renally cleared dmgs. 

The concept of protein modification by PEGylation is now well established clinically (5,136,137), and is used to increase protein solubility and stability, reduce immunogenicity, prevent rapid renal clearance of small proteins, and prevent receptor-mediated clearance by cells of the reticuloendothelial system. Many HPMA copolymer-antibody, -protein, and-peptide conjugates have also been synthesized (Table 2). In the main, protein incorporation has been used to promote cell-specific drug targeting, but conjugates of biologically active proteins, enzymes and coiled-coil peptide domains have also been reported. 

NRTIs are water soluble, and are mainly eliminated by the kidneys (di-danosine, lamivudine, stavudine, and zalcitabine) or undergo hepatie glu-curonidation (abacavir, zidovudine). The few important interactions with these drugs primarily involve altered renal clearance. For zidovudine (and possibly abacavir) some interactions occur via altered glucuronidation, but the clinical relevance of these are less clear (e.g. rifampicin , (p.792)). Cytochrome P450-mediated interactions are not important for this class of drugs. 

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