The blood is filtered in the glomeruli at a rate of 120 ml/min. All small molecules with molecular weight below 2000 can be filtered freely in the glomeruli. Larger molecules can be filtered depending on their molecular size, however large protein molecules such as albumin cannot be filtered. So, drug molecules that are bound to plasma protein cannot be filtered and only free drug molecules can be filtered.

The rate of plasma filtration in the glomeruli is 120 ml/min and is called the glomerular filtration rate. The rate of drug filtration in the glomeruli is the product of the free (unbound) drug concentration in plasma and the GFR (i.e. fu Cp . GFR ).

Reduced kidney function leads to lower glomerular filtration rate. Also, some diseases (e.g. nephrotic syndrome) can affect the glomerular filtration process and allow the filtration of larger protein molecules such as albumin, and globulins.

Drug molecules can be actively secreted in the proximal renal tubules. There are specific transport systems for different chemicals in the renal tubules. These transport systems actively secrete the drug molecules from the plasma to the lumen of the nephron.

These transport systems are not specific, however they can transport compounds with similar characteristics. So, drugs can compete with each other for the transport system, and drugs with higher affinity for the transport system can inhibit the secretion of other drugs with lower affinity. (e.g. probenecid inhibits the active secretion of penicillins in the renal tubules).

Since most of the water filtered in the glomeruli is reabsorbed in the renal tubules, the drug concentration in the nephron lumen is always higher than the plasma drug concentration. So, the drug secretion in the renal tubule is against the concentration gradient.

Drugs and solutes filtered in the glomeruli or actively secreted in the proximal tubules can be reabsorbed throughout the tubules. This reabsorption process can be passive or active.

Because of the water reabsorption in the renal tubules, solutes become very-concentrated and can be reabsorbed passively into the blood stream. Lipophilic molecules can cross the tubular membrane and can be reabsorbed easier than hydrophilic molecules. Ionizable molecules can be reabsorbed better when they are in their unionized form compared to their ionized form. So, the reabsorption and urinary-secretion of ionizable molecules can be modified by changing the urinary pH.

Some vitamins, amino acids and glucose can be reabsorbed by an active saturable transport system

The therapeutic range is defined as the range of plasma drug concentrations in which the probability of the desired therapeutic effect is high and the probability of the unacceptable toxicity is low. The lower limit of the therapeutic range is the minimum effective concentration (MEC) and the upper limit of the therapeutic range is the minimum toxic concentration (MTC).

The therapeutic range represents a range of drug conc in plasma and not at the site of action. This means that when the plasma conc of the drug is within the therapeutic range, the drug conc at the site of action (may be lower or higher than the plasma conc) produces the desired therapeutic effect.

The therapeutic range is different for different drugs. When the therapeutic range is wide, the drug is said to have a large therapeutic index, while when the therapeutic range is narrow, it is said that the drug has small therapeutic index. Drugs with small therapeutic index require careful selection of the dosing regimen to achieve therapeutic drug concentration.