Sometimes therapeutic equivalence may be achieved despite differences in bioavailability. In contrast, bioavailability differences are important for a drug with a relatively narrow therapeutic index. The physiologic characteristics and comorbidities of the patient also affect bioavailability. Absorption rate is important because even when a drug is absorbed completely, it may be absorbed too slowly to produce a therapeutic blood level quickly enough or so rapidly that toxicity results from high drug concentrations after each dose. Causes of Low Bioavailability When a drug rapidly dissolves and readily crosses membranes, absorption tends to be complete, but absorption of orally administered drugs is not always complete.
Many drugs have low oral bioavailability because of extensive first-pass metabolism.
For drugs with an active metabolite, the therapeutic consequence of first-pass metabolism depends on the contributions of the drug and the metabolite to the desired and undesired effects. Low bioavailability is most common with oral dosage forms of poorly water-soluble, slowly absorbed drugs. More factors can affect bioavailability when absorption is slow or incomplete than when it is rapid and complete, so slow or incomplete absorption often leads to variable therapeutic responses. Insufficient time in the GI tract is a common cause of low bioavailability. Ingested drug is exposed to the entire GI tract for no more than 1 to 2 days and to the small intestine for only 2 to 4 h.