Chemical (lipophilicity, size) and biological (species, genetics).

The COOH group can be changed to a tetrazole group to increase the drug's lipophilicity. Both groups have a similar pKa value so the ionisation of the molecules should be similar.

Yes. When substances are lipophilic (hydrophobic), they are usually much more easily retained in fat in the body, reducing its elimination rate. This allows for such substances (such as lipophilic vitamins) to accumulate in the body to toxic levels.

fat-solube is another name for lipophilicity a ability of a chemical compound to dissolve in fat,oils,lipids,and fat-solube non-polar solvents like hexane

It depends on the intrinsic properties of the drug and the route of administration. Oral drugs are often absorbed from the GI tract into the hepatic portal vein, undergo first pass, and then reach the systemic circulation.

They can be biotransformed (metabolized) in the liver, kidneys or even lungs. Most drugs are excreted by the kidneys into the urine, but some are excreted into bile by the liver.

Blood flow to particular organs, and the relative lipophilicity of the drug affect how it will behave in the body. It's metabolism is also key in figuring out how it will be excreted.