Bioavailability of a Drug:
When a drug is administered
intravenously (injected directly into the vein), the entire amount reaches the
target organ via the blood. However,
when a drug is administered orally, a number of factors reduce the total amount
of drug finally reaching the circulation and exerting its effect. The
amount of drug that reaches the circulation is called bioavailability of the
When a tablet is taken
orally, it first has to dissolve in the stomach and intestinal juices. It then gets absorbed through the lining of
the intestines or the stomach in some cases to reach the blood. The blood carries it to the liver, where
some amount of the drug may be destroyed.
Finally, the drug reaches the circulation, from where it goes to the
Thus, a number of factors can interfere with the bioavailability of a
drug. Food is one such factor. Many drugs are advised to be taken in a fasting state. This is because food reduces the absorption
of these drugs, and thereby the total amount available to take effect. In the case of some drugs however, presence
of food in the stomach actually increases the total amount absorbed. These drugs include griseofulvin,
mebendazole and halofantrine. These
drugs are advised to be taken with meals.
Oral Anticancer Drugs:
Anticancer drugs are usually
administered via injection. Nowadays, some anticancer drugs are
available for oral use. These include
lapatinib, erlotinib, nilotinib, gefitinib, abiraterone acetate and
sorafenib. These drugs are
convenient for the patient to take, and to avoid excessive injections. They could pose some problems in terms of
compliance - the patient may miss doses, which could lead to inadequate
Most oral anticancer drugs are advised to be taken in the fasting
state. One would presume that food reduces the
bioavailability of these drugs. This is
true for some drugs, for example sorafenib.
However, the same is not the
case with all the oral anticancer drugs that are advised to be taken in the
fasting state. Abiraterone acetate is a drug whose bioavailability actually increases
when taken with food. The same is observed
with other anticancer drugs like lapatinib, erlotinib and nilotinib. However,
the FDA still advises to take the drugs on an empty stomach. This is in contrast to the advice given in
cases of non-cancer drugs. In the case
of non-cancer drugs, if food increases the bioavailability of the drug, the
drug is advised to be taken with food.
Taking oral anticancer drugs with increased bioavailability along with
food has the following advantages:
more drug is absorbed into the blood, the total amount of unabsorbed drug in
the digestive tract is reduced, thereby reducing digestive tract side effects.
dose of the drug can be reduced; thus drug wastage is reduced and treatment
becomes more cost-effective.
the timing of the dosage with a meal may serve as a reminder for the patient to
take the drug.
It is hoped that the FDA will consider the unnecessary wastage of oral
anticancer drugs caused by taking them in fasting state and will review the
guidelines for taking these medications.
Peter Kang and Mark J. Ratain.
Inconsistent labeling of food effect for oral agents across Therapeutic
Areas: Differences between Oncology and
Non Oncology Products. Clin Cancer Res
2. Mark J. Ratain. Flushing Oral
Oncology Drugs Down the Toilet. Journal
of Clinical Oncology, Vol 29, No 30 (October 20), 2011: pp 3958-3959