**7.4. Placental barrier**

Tight junction

Epithelial cells which are in contact with the brain ventricular spaces form a barrier to the movement of drugs. These epithelial cells are connected by occluding zonulae (blood- brain barrier) as shown in Figure 3. The zonulae severely restrict the passage of most molecules between the bloodstream and the parenchyma of the central nervous system. Drug entry across this barrier is through

Epithelial cells which are in contact with the brain ventricular spaces form a barrier to the movement of drugs. These epithelial cells are connected by occluding zonulae (blood- brain barrier) as shown in Figure 3. The zonulae severely restrict the passage of most molecules between the bloodstream and the parenchyma of the central nervous system. Drug entry across this barrier is through either passive diffusion or carrier mediated transport. Only the lipid

Epithelial cells that separate the CSF from the brain are connected with tight junctions and are characterized by marked scarcity of pinocytic vesicles. However, the epithelial cells that lines the brain are not connected by occluding zonulae and therefore, there is unrestricted passage of drug molecules from CSF to the brain. Drugs like penicillin which are not much lipid-soluble and required in high concentrations for the treatment of brain abscesses are administered through intrathecal injections directly into the CFS.

The placental membrane limits the amount of maternal blood following through the placenta to the foetus and passive diffusion is the main mechanism of drug entry from the maternal blood to the foetus. The shortest time required for equilibration of a drug between mother and foetus is about ten minutes and this delay is useful as it can allow a mother to be anaesthetized during final

A drug will reach systemic arterial circulation only if it is absorbed from the GIT and if it escapes metabolism in the gut, liver, and lungs. When the concentration of the drug in plasma is measured at specified time intervals, it is possible to construct

Epithelial cells that separate the CSF from the brain are connected with tight junctions and are characterized by marked scarcity of pinocytic vesicles. However, the epithelial cells that lines the brain are not connected by occluding zonulae and therefore, there is unrestricted passage of drug molecules from CSF to the brain. Drugs like penicillin which are not much lipid-soluble and required in high concentrations for the treatment of brain abscesses are administered

The availability depends on both the extent of absorption and the extent of presystemic metabolism and comprises three aspects; Peak concentration (Cmax), Time taken to reach the peak (Tmax) and area under the curve (AUC)as shown in Figure 4. The Cmax and Tmax are measures of the rate of availability while AUC is a measure of the extent of availability (i.e. proportion of the administered

concentration versus time graph and hence be able to determine the extent of drug availabilityas shown in Figure 4.

either passive diffusion or carrier mediated transport.Only the lipid soluble drugs cross into the CSF from blood.

Figure 2. Arrangement of epithelial cells with tight junctions

482 Drug Discovery

**Figure 2.** Arrangement of epithelial cells with tight junctions

soluble drugs cross into the CSF from blood.

**7.3. Cerebrospinal fluid barrier (CSF)** 

**7.3. Cerebrospinal fluid barrier (CSF)**

Figure 3. Epithelial cells with tight junctions as part of the blood brain barrier

**Figure 3.** Epithelial cells with tight junctions as part of the blood brain barrier

through intrathecal injections directly into the CFS.

**7.4. Placental barrier** 

**8. Systemic availability of drugs** 

stages of labour.

cells

The placental membrane limits the amount of maternal blood following through the placenta to the foetus and passive diffusion is the main mechanism of drug entry from the maternal blood to the foetus. The shortest time required for equilibration of a drug between mother and foetus is about ten minutes and this delay is useful as it can allow a mother to be anaesthetized during final stages of labour.
