Drug Class
Generic Name
(Trade Name)
Absorption
Distribution
Elimination Alkylating Agents
melphalon
(Alkeran)
oral - variably and incompletely absorbed from the GI tract, decreased in presence of food
moderately high protein binding, Vz 0.5 l/kg
deactivated in plasma by hydrolysis
cyclophosphamide
(Cytoxan)
oral - high bioavailability; intravenous
crosses blood-brain barrier (limited)
hepatic biotransformation (includes activation); 5 - 25% eliminated unchanged (renal); parent and metabolites eliminated in urine are toxic to bladder
ifosfamide
(Ifex)
intravenous infusion only
active metabolites cross blood-brain barrier (limited)
hepatic biotransformation (includes activation); 10 - 60% eliminated unchanged (increases with increasing dose - renal); parent and metabolites eliminated in urine are toxic to bladder
busolfan
(Myleran)
oral - completely absorbed from GI tract
rapid hepatic biotransformation
procarbazine
(Matulane)
oral - Rapidly and completely absorbed from the gastrointestinal tract.
Crosses blood-brain barrier.
Hepatic biotransformation, very short elimination half-life. 70% renal elimination as metabolites.
dacarbazine
(Otic-Dome)
Intravenous only
limited access to CNS; low protein binding
Extensive hepatic biotransformation; 50% renal elimination (1/2 unchanged).
Antibiotics
daunorubicin
(Cerubidine)
intravenous only
body water, excluded by blood-brain barrier
hepatic metabolism produces both active and inactive metabolites.
daunorubicin or doxorubicin liposomes
(Daunoxome or Doxil)
intravenous infusion only
limited to vascular fluid, animal studies indicate delivery to CNS; tissues selectively "acquire" liposomes.
greatly reduced hepatic metabolism compared to un-encapsulated drug
doxorubicin
(Adriamycin)
intravenous only
high protein binding; extensive uptake into many tissues, does not cross blood-brain barrier
hepatic metabolism produces both active and inactive metabolites; tissue metabolism results in production of free radicals.
idarubicin
(Idamycin)
intravenous infusion only
extensive tissue binding of both native drug and metabolite; very high plasma protein binding
hepatic and extrahepatic metabolism to equipotent metabolite; elimination primarily biliary as active metabolite.
plicamycin
(Mithracin)
intravenous infusion only
crosses blood-brain barrier, concentrated in Kupffer cells, renal tubular cells and bone surfaces
elimination is renal
mitomycin (Mutamycin)
intravenous only
does not cross blood brain barrier
hepatic biotransformation, 10% eliminated in urine unchanged (% increases as dose increases)
pentostatin
(Nipent)
intravenous only
crosses blood-brain barrier (CSF concentrations ~10% of plasma concentrations within 24 hours). Low plasma protein binding
hepatic biotransformation, 30% - 70% eliminated in urine as unchanged drug
mitoxantrone
(Novantrone)
intravenous infusion only
rapid extensive distribution to tissues; high protein binding
hepatic; long half-life (due to tissue binding & slow metabolism); small fraction eliminated unchanged.
dactinomycin
(Cosmegen)
intravenous only
does not cross blood brain barrier
Minimal biotransformation; Elimination primarily biliary/fecal 50% unchanged (24 hours), another 10% unchanged in urine (24 hour); remainder of the drug is recovered within 1 week.
Antimetabolites
fluorouracil
(Adrucil)
intravenous only
good tissue penetration, crosses blood brain barrier
hepatic metabolism produces 2 active metabolites and catabolism; respiratory elimination as carbon dioxide; 7 - 20% unchanged in urine
capecitabine
(Xeloda)
oral (pro drug)
as for fluorouracil
hepatic activation by conversion to 5 fluorouracil; elimination pattern as for 5 flurouracil
fludarabine
(Fludara)
intravenous only
distributed to whole body water
RAPIDLY dephosphylated in serum to 2-fluoro-Ara-A, then phosphorylated intracellularly to active compound. Elimination is renal, approximately 20% unchanged 2-fluoro-Ara-A
mercaptopurine
(Purinethol)
oral - variably and incompletely absorbed from the GI tract (up to 50%)
Crosses blood-brain barrier but poorly; low protein binding
Hepatic metabolism for both activation and catabolism; degraded by xanthine oxidase; 7 - 40% eliminated unchanged.
gemcitabine
(Gemzar)
intravenous infusion only
distribution of active metabolite is limited by saturable process. Giving gemcitabine at an excess rate WASTES drug (eliminated intact before conversion).
Intracellular metabolism (saturable) to active metabolites. Hepatic deamination to inactive uracil metabolite.
Hormonal Oncologics
topotecan
(Hycamtin)
intravenous infusion only
good tissue penetration, volumes approximately 2x body water, crosses blood brain barrier
reversible pH-dependent hydrolysis to inactive moeity (low pH favors active compound), hepatic metabolism insignificant; 30% eliminated unchanged in urine
leuprolide
(Lupron)
IM injection - 90% bioavailability; 1 month, 3 month and 4 month release formulations
distributed to extracellular fluid volume; moderate (50%) protein binding.
Metabolized to several inactive peptides. Less than 5% recovered as parent or pentapeptide metabolite.
tamoxifen
(Nolvadex)
oral administration, bioavailability?
?
Hepatic biotransformation with enterohepatic circulation. Prolonged elimination; Elimination primarily biliary/fecal, mostly as metabolites
Mitosis inhibitors
etopside
(VP16)
oral - variable dose-dependent oral bioavailability (F decreases as dose increases); intravenous
Low and variable into CSF, concentration differentials between normal and cancerous tissues. Very high protein binding (97%). Protein displacement interactions and hypoalbuminemia are concerns.
Hepatic biotransformation; up to 50 - 60% renal elimination (2/3 as unchanged drug); remainder fecal.
Others
hydroxyurea
(Hydrea)
Well absorbed following oral administration.
Crosses the blood-brain barrier (very small molecular weight).
Hepatic metabolism (inactivation), 80% renal elimination within 12 hours (50% unchanged); balance eliminated from lungs as CO2
paclitaxel
(Taxol)
intravenous only
extensive extravascular distribution and/or tissue binding. Very high plasma protein binding.
Hepatic p450 metabolism. Elimination primarily biliary / fecal. Variable renal elimination of unchanged drug.
docetaxel
(Taxotere)
intravenous only
widely distributed in tissues; slightly larger than body water; poor CNS penetration.
Hepatic p450 metabolism. Elimination primarily biliary / fecal.
cisplatin
(Platinol)
intravenous only
does not penetrate CNS
rapid non-enzymatic conversion to inactive metabolites. Elimination usually expressed as recovered platinum (only 50% after 5 days), platinum detected in tissues for months.
aspariginase
(Elspar)
intravenous
intramuscular
slow sequestration by reticuloendothelial system; poor CNS penetration
unknown pathway, only trace amounts appear in the urine following IV administration.
Anti-toxicity
amifostine
(Ethyol)
intravenous infusion only
wide rapid distribution
metabolised by alkaline phosphatase to active free thiol metabolite (binds cisplatin metabolites and alkylating agents and scavanges free radicals. Reaction favored in normal tissues (higher AP)
dexrazoxane
(Zinecard)
intravenous only
distributed to whole body water, low protein binding
several hepatic metabolites, intracellular metabolite may be responsible for action though this is speculative at this time
mesna
(Mesnex)
intravenous only
volume of distribution approximates body water.
rapid hepatic biotransformation to mesna disulfide; mesna disulfide is reduced to mesna by renal tubular epithelium, mesna binds and detoxifies metabolites of oxazophosphorines.
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Antidepressants, alcohol, cocaine
some of the drugs can cross blood-brain barrier, so it can affect neurons too.
Lipophilic drugs such as diazepam and heroin cross the blood-brain barrier most easily due to their ability to dissolve in lipid membranes.
Drugs which are administered percutaneously, sublingually, or have to cross the blood brain barrier have to be lipophilic.
The blood-brain-barrier.
The blood-brain barrier is an actual filter. Most molecules are too big to squeeze through it! This protects the delicate brain cells from a lot of toxins and poisons. It also keeps some chemicals inside the brain, where they can act to the most good.
Meningitis, by definition, is an inflammatory process of the meninges, which constitute the blood brain barrier (BBB). Inflammation makes the blood brain barrier more permeable to chemicals, such as antibiotics. Under normal circumstances, penicillin does not cross the BBB very well, but when inflamed, it can cross more readily.
The placenta acts as a barrier to many drugs due to its structure and functions similar to the blood-brain barrier. It is designed to protect the developing fetus from harmful substances while allowing essential nutrients to pass through. This barrier prevents many drugs from crossing into the fetus's bloodstream during pregnancy.
Oxygen, carbon dioxide, glucose, and certain lipid-soluble molecules like alcohol and caffeine can pass through the blood-brain barrier. Furthermore, some other substances like certain drugs may also be able to cross the barrier with the assistance of specialized transport mechanisms.
The blood brain barrier is effective again harmful chemicals in the blood and bacteria infections from reaching the brain. Many of the drugs on the street breach this barrier. K12 or bath salts is a very good example of the damage breaching this barrier can cause.
The Blood-Brain Barrier (BBB). This is actually a good website describing it : http://faculty.washington.edu/chudler/bbb.html
Yes, the brain has anatomical barriers that limit the entry of drugs. The blood-brain barrier (BBB) is a highly selective barrier formed by specialized endothelial cells that line the blood vessels in the brain. It prevents the passage of certain substances, including many drugs, from entering the brain tissue. The liver also has its own protective barriers, such as the hepatocyte membrane, which regulates the absorption and distribution of drugs.