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[PubMed: 29663652] 84

Passive tubular reabsorption with important considerations including: Enhanced lipid solubility favors reabsorption (lipid-soluble agents more readily cross renal tubular epithelial cell membrane thus entering pericapillary fluid) Example: thiopental (highly lipid-soluble): completely reabsorbed -- minimal unchanged drug excreted in urine Renal tubular reabsorption rate influenced by: pH Rate of renal tubular urine flow Weak acid or weak base drug/drug metabolite pKa compared to urinary pH Hepatic clearance: drug elimination following metabolic transformation of the parent drug to metabolites Since elimination is not "saturable", elimination is typically first order and directly proportional to drug concentration: Rate of elimination = CL x C Other factors affecting renal clearance Renal disease Rates of filtration depend on: Volume filtered in the glomerulus Unbound drug concentration in plasma (plasma protein-bound drug is not filtered) Drug secretion rates: Extent of drug-plasma protein binding Carrier saturation Drug transfer rates across tubular membranes Rate of drug delivery to secretory sites Changes in plasma protein concentration Blood flow Number of functional nephrons Factors affecting hepatic clearance: Drug delivery to hepatic elimination sites may be rate-limiting for certain drugs: Also called flow dependent elimination: in this case most of the drug in the blood is eliminated on the first pass of the drug through the organ Ahese drugs are termed "high-extraction" Extent of plasma protein-bound drug Blood flow (affects clearance on drugs with high extraction ratios)

PMID 18566306

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