Pharmacokinetics (Pk) - Routes of administration of drugs

Pharmacokinetics

Pharmacokinetics is the quantitative study of drug movement in, through and out of the body. Pharmacokinetics deals with the movement of drugs. A drug that is administered must be absorbed, distributed, metabolized and excreted. Pharmacokinetics deals with absorption, distribution, metabolism and excretion of drugs. In simple words it is described as what the body does to the drug. The intensity of response is related to concentration of the drug at the site of action, which in turn is dependent on its pharmacokinetic properties. Pharmacokinetic considerations, therefore, determine the route of administration, dose, latency of onset, time of peak action, duration of action and frequency of administration. Pharmacokinetic information is helpful in determining and adjusting the drug dosage schedules and in interpreting drug concentration data. A drug that is administered must move through different parts of the body and for this movement it must pass through various membranes.

            Drug Administration

            For a drug to act and produce its characteristic systemic effects, it must first be absorbed and then attain an effective concentration at its site of action (Biophase). Absorption is the movement of drug from the site of administration to circulation. Not only the fraction of the administered dose that gets absorbed, but also the rate of absorption is important. Except with intravenous administration, the drugs have to cross the biological membranes for entering the systemic circulation.

Factors affecting absorption in general include - aqueous solubility, concentration of the drug, area of the absorbing surface, vascularity of the absorbing surface and route of administration.

Routes of administration

Absorption of a drug is very much depending on the routes of administration. Routes of drug administration can be broadly divided into two categories: 1. Topical, 2. Systemic administration.

The choice of the route and technique of administration is generally based on several factors viz.,

a.     physicochemical properties of drugs & the formulation to be used,

b.    the therapeutic indication (site of desired action),

c.     the physiopathology of the disease condition,

d.    species of animal involved,

e.     ease of handling & controlling the animal,

f.     rate and extent of absorption of the drug from different routes,

g.    rapidity with which the response is required,

h.     accuracy of dosage required,

i.      condition of the patient &

j.      economic factors – repetitive dosing or mass medication of a herd / flock.

Topical Application of drugs:

Drugs are placed directly on to the affected site as cream / ointment on skin and mucous membrane or drops in ears, eyes; in rare instances a drug impregnated patch is placed on to skin for gradual absorption. Application of drugs on the skin and mucous membrane is useful for localized effect.

            Topical administration of drugs is restricted to readily accessible organs and structures such as skin, eyes, ears, body orifices, body cavities and mammary glands. Many dosage forms (ointment, cream, paste, dusting powder, lotion, spray, liniment, poultice, gargle, plasters, etc.) have been developed to deliver active principles to the site of application in order to produce local effects. Absorption through the skin can also be enhanced by occlusive dressings, inunction (suspending the drug in oily vehicle and rubbing the resulting preparation in to the skin) or the use of Di Methyl Sulphoxide (DMSO) as a carrier. Several drugs are deliberately applied to the skin with the anticipation of systemic effects following transdermal absorption. E.g., External parasiticides available as “Pour on” formulations, medicated ear tags, nitroglycerines ointment, and a transdermal patch device-containing scopolamine.

            Drugs are applied locally to mucous membranes (eyes, mouth, throat, urethra, vagina, rectum, bladder) to achieve anti-infective, anti-inflammatory, decongestant, astringent, or anaesthetic effects. Drugs forms most frequently administered by the mucosal route include solutions, suspensions & suppositories. Less commonly used forms include creams, ointments, tablets, powders, sponges and tampons. Intra mammary infusion of ointments containing antibacterial & anti-inflammatory agents is frequently employed for the treatment of bovine mastitis.

Commonly used dosage forms for dermal application include ointments, creams, pastes, dusting powders, lotions, sprays, liniments and poultices. Specialized dosage forms like "pour-on", "spot-on" formulations, medicated ear tags, collars, transdermal patches are also available. Dusting powders and solutions are useful for superficial activity. Oily ointments enhance the penetration of drugs into the dermis and lipophilic substances can pass through the skin. Absorption can be increased by inunction (rubbing with friction) or iontophoresis (Ionisable drugs may be made to penetrate into deeper tissues by the help of galvanic current where they may be taken up by blood stream and act particularly on tissues in the neighborhood of the point of application. Such method of administration of drugs is known as Iontophoresis). DMSO (dimethylsulphoxide) facilitates penetration through the skin. Damaged, inflammed and hyperemic skin allows drugs to pass through readily. In general, skin is an efficient barrier and little systemic absorption of topically applied drugs is seen. Systemic absorption from such a site will vary with the nature of the drug, characteristics of the vehicle and the degree of hydration of the stratum corneum of the skin and the location. However, organophosphorous insecticides in cattle and organochlorine insecticides in cats constitute a considerable toxic hazard. Topical application should be used with particular care in cats because of their extensive grooming habits. Drugs are rapidly absorbed through wounds. Transdermal delivery systems release drug through a rate controlling membrane into the skin and so into the circulation. Fluctuations in plasma concentration associated with other routes of administration are largely avoided, as is first-pass elimination in the liver. These are in the form of adhesive patches of various sizes and shapes. The drug is held in a reservoir between an occlusive backing film and a rate controlling micropore membrane, the under surface of which is smeared with an adhesive impregnated with priming dose of drug that is protected by another film to be peeled off just before application.

For application on the mucus membrane preparations available include solutions, suspensions, suppositories or pessaries, creams, ointments, powders, sponges and tampons. Drugs can be applied on the oral, nasal, conjunctival, vaginal, rectal and urethral mucous membrane for local effect. Intra mammary administration is useful when localized therapy is needed as in mastitis. However, absorption into systemic circulation may occur following intramammary administration depending on the pKa of the drug and pH of milk. Dosage forms used for intramammary administration include solutions and creams.

Some special preparations are specifically administered into the certain body cavities. E.g. Bougies – urethra; pessaries – uterus; douches – vegina; suppository – rectum.

Ophthalmic preparations

These are the solutions for administration in to the eye. For prolonged effect Lamellae, occulenta or as powders for local action on the conjunctiva.

Advantages: Usually simple and convenient; usually painless; safest route of administration, unless there is a major hypersensitivity reaction; drug is administered directly on the site of action; drug concentrations at the at the site of action can be 100s – 1000s of times greater than the maximum concentration that could be achieved at the site following I.M. / oral / I.V. administration; No significant absorption, hence, no systemic effects.

            Disadvantages: only possible for a limited number of conditions that require drugs; may be quite messy and stain clothing and skin; some topical drugs wash off easily and do not last long; systemic effects may occur due either to licking of the applied medication / to percutaneous drug absorption, which often takes place especially when the skin is damaged / inflammed (burns, ulcers, wounds, dermatitis, etc.).

 

Systemic administration

            This is classified into two broad categories: 1. Enteral & 2. Parenteral routes of administration.

            Enteral route of administration: here the drug is placed directly in the GIT either by placing it under the tongue (sublingual route of administration) or by swallowing (oral route of administration) or by rectal administration.

Oral administration: Drug is given by mouth and swallowed. Usually called as “per os”; abbreviated “P.O.” on medical records. It is the most common route of administration. In some situations drug may be given by stomach tube. Common Dosage forms available for oral use include powders, tablets, enteric-coated tablets, capsules, granules, syrups, electuaries, solutions, suspensions, and pastes. Powders, granules, and pellets, and soluble powders and liquid forms are used for medicating feeds and drinking water, respectively. In these preparations a variety of inert fillers, binders, lubricants, disintegrants, vehicles, and diluents are used. These adjuvants and excipients may influence the chemical stability of the formulation and the drug’s clinical effectiveness. The rates of disintegration and dissolution of solid dosage forms within the GIT are also determined by these ingredients and may vary between different manufacturers’ products. Such discrepancies in pharmaceutical availability lead to generic or therapeutic inequivalence between supposedly identical preparations. This problem is now well recognized and in large measure has been rectified by regulatory requirements.

In addition to the standard dosage forms, a number of specialized delivery systems are also available. These include enteric-coated tablets and sustained-action or controlled-release preparations. These time-release formulations provide delayed or gradual escape of active ingredient in several ways. The methods include micro encapsulation, embedding in a slowly eroding matrix or inert carrier, formation of poorly soluble chemical complexes, and the use of ion-exchange resins.

Orally administered drugs are exposed to low pH ranges, digestive enzymes, enteric microflora, and ingesta that vary greatly between species. Moreover, when a drug is absorbed from the stomach or intestinal tract it enters the portal circulation and passes through the liver before reaching the systemic circulation. During this time a high degree of metabolic transformation may occur – the “First pass” effect / pre-systemic metabolism.

Although some oral solutions, either elixir or aqueous and suspensions are available, most oral dosage forms are solids include tablet, bolus for large animals, pellets, capsule and a variety of specialized sustained-release products for ruminant animals. Before entering the systemic circulation a drug administered as a solid dosage form must undergo three events. 1) Release from the dosage form (dissolution), 2) transport across the gastro intestinal mucosa, 3) passage through liver. Each of these events has the potential to decrease the amount of drug reaching the circulation intact (unchanged). The net effect is reflected in the bioavailability profile.

            Dissolution is the rate-limiting step that determines release of drug from a solid dosage form, and it frequently controls the rate of drug absorption. The dissolution process can be enhanced by administering the drug in salt form or by decreasing the particle size, a technique called micronization (griseofulvin). Following its release, the drug in solution must be stable in the environment with in the stomach (reticulorumen) and small intestine and must be sufficiently lipid soluble to diffuse through mucosal barrier to enter the hepatic portal venous blood. A drug that is stable (neither chemically nor enzymatically inactivated) in gastrointestinal fluids, not completely ionized, and lipid soluble would be expected to be completely absorbed.

            The rate of gastric emptying is the most important physiologic factor controlling drug absorption rate, since the small intestine is the principal site of absorption.

            Despite the stratified squamous nature of its epithelial lining, the rumen has been shown to have considerable absorptive capacity. Rumen P^H 5.5-6.5, high concentration of volatile fatty acids, buffers secreted in alkaline saliva (PH 8.0 to 8.4) and drug appear directly by fore stomach epithelium.

            Owing to large volume of ruminal fluid, a drug can attain only a low concentration in this organ, whether it is given in solution or as a solid dosage form. Non – ionized, lipid soluble form of weak organic acids in particular should normally be well absorbed from the rumen. Indigenous micro flora may inactivate certain drugs by metabolic transformations of a hydrolytic or reductive nature. Chronic oral dosage with an antimicrobial agent can suppress micro flora activity and there by disturb carbohydrate digestion. Which is essential function of fore stomach.

Advantages: Convenient & safe procedure; Economical; Relatively simple for owner; No need for sterile equipment; Systemic distribution can be achieved; the danger of acute drug reaction is not great; Painless administration; Self administration is possible in humans; Absorption takes place in large surface area with rich blood supply.

Disadvantages: Absorption may be variable; Gastric irritation may cause vomiting; Not useful if animal is vomiting; Requires cooperation of patient; Drugs may be destroyed by gastric acidity, gut flora, mucosal enzymes and liver enzymes; Onset of effect is usually slow; Drug gets diluted in the voluminous ruminal contents; A larger dose is required; A transit time that may be modified by GI disturbances; Poor technique or the presence of dysphagia may lead to intratracheal delivery and subsequent bronchopneumonia; The extent to which orally administered drugs can elicit the oesophageal groove reflex determines the pH of the medium into which the drug enters; When antimicrobials are administered to ruminants orally for a longer duration of time, they may bring about an alteration in the microbial ecosystem of the rumen resulting in gastrointestinal disturbance.

Enteric coated preparations: Drugs that are destroyed by the gastric juice or that cause gastric irritation can be administered orally with a coating that prevents dissolution in the acidic gastric contents. It is important that they do dissolve once they reach the duodenum. Onset of drug action is considerably delayed with enteric-coated tablets.

Sublingual tablets: In this solid dosage form is place under the tongue, which is highly vascular and drug is absorbed slowly in the sublingual blood capillaries. E.g. Nitroglycerine. Not commonly used in veterinary practice. Absorption directly from the oral cavity is sometimes useful when a rapid response is required, particularly when the drug is either unstable at gastric pH or rapidly metabolized by the liver. Eg. Glyceryl trinitrate. Only drugs that are lipid soluble and non-irritating can be administered sublingually. Drugs absorbed by mouth pass directly into the systemic circulation without entering the portal system and so escape the first-pass metabolism. This type of tablet is useful in the treatment of angina pectoris where the drug enters directly into the systemic circulation and provides immediate effect. Once the required effect has been achieved, the excess tablet can be spit off.

Timed release preparations: Timed release preparations are designed to produce slow uniform release and absorption of the drug over a period of 8 hours or more. They are also known as spansules or timesules.

Advantages: Less frequent administration; Lasts overnight; Drug levels are more constant and do not peak after each administration (less toxic effects); Good for short-acting drugs

Disadvantages: Marketed preparations are sometimes not reliable; Dissolution rates may be irregular; Not needed for long acting drugs; Not good for a brief therapeutic effect

Rectal administration: This route of administration is useful when the animal is unconscious or vomiting. Rectal absorption is often incomplete and erratic. Drugs can be administered rectally in the form of enema or suppository. Irritant and unpleasant drugs can be administered per rectum. However, rectal inflammation may occur due to highly irritant drugs.50 percent of drug absorbed from rectum by pass liver. Many drugs cause irritation of the rectal mucosa. Rectal injections, Enemata is carried out to produce evacuation of bowels either with soap and warm water or as glycerin enema.

Parenteral administration: While considering parenteral administration, the points of importance include: 1. Volume to be administered; 2. Concentration of the drug; 3. pH; 4. Toxicity; 5. Viscosity;

6. Particle size if suspension is used; 7. Adjuvant used in the preparation

In general, parenteral administration requires skill and use of sterile equipment. Parenteral preparations are normally used as solutions or suspensions. Several novel approaches have been introduced for parenteral delivery of drugs like microspheres, microcapsules, liposomes, microsponges, resealed carrier erythrocytes and projectile biodegradable missiles. Additionally monoclonal antibodies have been utilized to carry highly selective bound drugs to specific target tissues or even cells.

Advantages over oral administration.

In some instances parenteral administration is essential for the drug to be absorbed in active form.

1. Availability is usually more rapid and more predictable than when a drug is given by mouth. The effective dose can therefore be more accurately selected.

2. In emergence therapy, Parenteral administration is particularly serviceable.

3. If a patient is unconscious, uncooperative or unable to retain any thing given by mouth, then the parenteral therapy may be necessary.

Disadvantages:

1.            Asepsis must be maintained.

2.            An intravascular injection may occur when it is not intended.

3.            Pain may accompany the injection and difficult to perform the injection by the owner.

4.            Expense. 

Parenteral injections

            Major routes of parenteral administration are intravenous (i/v), intramuscular (i/m), and subcutaneous (s/c). Absorption from s/c and i/m sites occurs by simple diffusion along the gradient from drug depot to plasma. The rate is limited by the area of the absorbing capillary membranes and by the solubility of the substance in the interstitial fluid. Relatively large aqueous channels present in the endothelial membrane are account for the indiscriminate diffusion of molecules regardless of their lipid solubility. Larger molecules, such as proteins slowly gain access to the circulation by way of lymphatic channels.

            Drugs administered into the systemic circulation by any route, excluding the intra-arterial route, are subject to possible first-pass elimination into the lung prior to distribution to the rest of the body. The lungs serve as a temporary clearing site for a number of agents, especially drugs that are weak bases and are predominantly nonionized at the blood PH, apparently by their partition into lipid. The lungs also serve as a filter for particulate matter that may be given intravenously.  Of course they provide a route of elimination for volatile substances.

Intravenous administration

Injection of a drug directly into the blood stream gives a more predictable concentration of the drug in plasma and produces immediate plasma concentrations, which can produce a pharmacologic response. The entire dose of the drug is administered directly into the systemic blood stream rather than being administered extravascularly and requiring the drug to be absorbed from the injection site into the systemic circulation. This is of major importance in emergency situations and for drugs, which may be irritant if injected into muscle or subcutaneous tissue. Except where a rapid onset of effect is required, i.v. injections are usually made slowly with constant patient monitoring. Slow infusions can be used to maintain the plasma concentration at some fixed level.

Advantages: Extremely rapid onset of action; Initial absorption step is by-passed; Drug levels can be controlled more accurately; Suitable for large volumes of drugs. Injection of a drug solution directly into the blood stream gives a predictable concentration of the drug in plasma and in most instances produces an immediate pharmacological response. I/v injection should be performed slowly except in special circumstances like induction of anesthesia by rapid introduction into the blood stream of small dose of thiopental as an i/v bolus. Surgical anesthesia by barbiturates, the dose of a drug is not predetermined but is adjusted to the response of the patient. Certain irritating solutions can be given only in this  manner. Since blood vessel walls are relatively insensitive, and the drug if injected slowly is greatly diluted by the blood, usually required for high molecular weight protein and peptide drugs.

Disadvantages: Most dangerous route as toxicity can easily occur (as a general rule even the injection of a small volume should be made over a period of one circulation time); Drugs must be in aqueous solution; Must be performed slowly; Once injected, drug cannot be removed; Drugs formulated as suspensions or oily solutions cannot be given by i.v.injection; with some drugs, problems with vein irritation may predispose to thrombus formation, which may also be associated with the presence of catheters. Repeated intravenous injections are dependent upon the ability to maintain a potent vein. Through this route, should not give drugs in an oily vehicle or those that precipitate blood constituents or hemolyse erythrocytes. Intravenous injections usually must be performed slowly and with constant monitoring of the response of patient.

Subcutaneous administration: This route is useful when slow and continuous absorption is required. The formulation must be isotonic and at physiological pH. Certain drugs that are irritating can cause severe pain and necrosis. The rate of distribution of the drug is largely dependent on blood flow and it can, therefore, be slowed by including a vasoconstrictor. Warmth or vigorous massage will increase distribution. Addition of hyaluronidase can enhance drug dispersion. This enzyme hydrolyses the hyaluronic acid polymers, which comprises the intercellular cement and thus facilitates diffusion through the tissues. Specialized subcutaneous preparations include dermojet and pellet implantation. Dermojet is a process where no needle is used. A high velocity jet of the drug solution is projected from a microfine orifice using a gun like implement. The solution passes through the superficial layer and gets deposited in the subcutaneous tissue. It is essentially painless and suitable for mass inoculation. Pellet implantation provides sustained release of the drug over weeks or months. The pellet impregnated with the drug is implanted in the subcutaneous tissue. Sialistic (non biodegradable) and biodegradable implants are used. Crystalline drug is packed in tubes made of suitable material and implanted under the skin. Constant blood levels can be maintained as the drug is released uniformly over a period of time. If non-biodegradable implant is used, it should be removed after the specified period of time. It can be used only for drugs that are not irritating to tissue; otherwise sever pain, necrosis and slough may occur. Rate of absorption often is sufficiently constant and slow to provide a sustained effect. Moreover, it may be varied intentionally. For example the rate of absorption of a suspension of insoluble insulin is slow compared with that of soluble preparation. The incorporation of vasoconstrictor agent in a solution of a drug to be injected s/c also retards absorption. Absorption of drugs Implanted under the skin in a solid pellet form occurs slowly over a period of weeks or months. Some hormones are effectively administered in this manner.

Hypodermoclysis It is special process of infusing large amount of drugs like glucose and saline through loose subcutaneous tissues of the body.

Intramuscular administration: Drugs in aqueous solution are rapidly absorbed after intramuscular administration. However, very slow constant absorption occurs if the drug is administered in oil or suspended in other repository vehicles as depot preparations. It can be used for relatively irritant drugs and such drugs must be administered deep intramuscularly. Intramuscular injections are always painful and large volumes cannot be injected. A disadvantage of this route is the possibility of improper deposition in nerves, blood vessels, fat or between muscle bundles & in connective tissue sheaths. Whenever drugs are administered intramuscularly, it is always advisable to confirm that the needle is not in the blood vessel.

Intraarterial: Occasionally a drug is injected directly into artery to localize its effect in a particular tissue or organ. Sometimes, diagnostic agents are administered through this route. It required great care and should be reserved for experts. The first pass and cleansing effects of lungs are not available. 

Intra peritoneal administration: This route is particularly useful in laboratory animal medicine and neonatal animals and for the administration of large volumes. There is a very large absorbing area and absorption is rapid. Absorption is via the portal system, so it is not useful for drugs that are removed by the liver. There is danger of infection and peritoneal adhesions are not uncommon. So it is not used routinely. Peritoneal dialysis is becoming more frequently used in small animals with short-term renal failure and renal insufficiency.

Intra dermal administration: Drug is given within the skin layers (dermis).This route is used mainly for diagnostic purposes e.g. for Tuberculine testing in cattle and also   for   hypersensitivity   testing   before   administering   some   drugs   known   to   induce hypersensitivity. This route is used for testing sensitivity to drugs. E.g. penicillin, antitetanus serum (ATS), tuberculin test. Absorption is through lymphatics. Thus intradermal sensitivity test gives a clue as to whether drug to be injected would be safe or allergic in nature for the concerned patient. Highly diluted and small quantity of drug is administered even this is painful

                Intra thecal administration: Blood brain barrier (BBB) and blood cerebrospinal fluid barrier often preclude or slow the entrance of drugs into the CNS. Therefore, when local and rapid effects of drugs on the meninges or cerebrospinal axis are desired, as in spinal anesthesia or acute CNS infections, then the drugs are injected directly into the spinal subarachnoid space. In this route the drug is administered through the membranes enclosing the central nervous system in the lumbar area or into the cisterna magna. It is occasionally used for radiographic examinations and chemotherapy of central nervous system infections and neoplasms.

Epidural administration: Drug solutions are injected on and around the duramater for inducing local or regional anesthesia without involving the CNS. This route is mainly used to anaesthetize animals for surgery like parturition in cattle. The drug is administered between the first and second coccygeal vertebrae.

Intra articular administration: This route is used to administer antiinflammatory agents into the joint capsule.

The other parenteral routes of drug administration rarely used are intra medullary, intra testicular, intra cardiac etc.

Respiratory system: This is the site of absorption of atmospheric pollutants. Volatile anaesthetics are administered by inhalation. Absorption is very rapid as the alveoli have an enormous surface area and is rich in blood supply. Drugs that can be nebulized can be given by inhalation, but particle size is extremely important for efficient administration. Ideally particles should be less than l mm in diameter. Inhalation therapy is useful for administering drugs that are poorly absorbed from other route. Thus, lung infections can be treated with high, localized concentrations of antibiotics and bronchoconstriction can be treated with corticosteroid levels that would normally have unacceptable side effects. Nasal administration of drugs is commonly practiced and drugs are readily absorbed through the nasal mucous membrane. They also by-pass the liver. Drugs can be applied as gases, vapours, snuff, spray, solution or nebulized solution. In addition, solutions of drugs can be atomized and the fine droplets in air (aerosol) inhaled.

Advantages

1)             Most instantaneous absorption of drug into the blood.

2)             Avoidance of hepatic first-pass loss.

3)             In the case of pulmonary disease local application of the drug at the desired site of action.

E.g. drugs can be given in this manner for the treatment of bronchial asthma.

Disadvantages

1)                              Poor ability to regulate the dose.

2)                              Cumbersomeness of methods of administration.

3)                              Many gaseous and volatile drugs produce irritation of the pulmonary epithelium.

Inoculation

            Pox vaccine is administered by superficial puncture or scaring of the epidermis. The vaccine drop is slowly absorbed by the lymphatics.

Intracardiac

            It is given quickly and directly in to the cardiac muscle in sudden stoppage of healthy heart (adrenaline in drowning). It is the last resort of defeated physicians to revive a stand still heart.

Intramedullary

            It is given in the medulary cavity of the bone when i/v is not possible. Glucose and saline solutions, plasma and blood transfusion etc. can be administered especially in  young animals.

Serous cavity injections

            To achieve local concentrations of drugs are injected in serous cavities, peritoneal, pleural, pericardial and articular cavities. Of these intra peritoneal injections are quickly effective because of the rich lymphatic supply in that region.

            Intra articular injections of antibiotics and carticosteroids are administered in inflamed joint cavities (rheumatoid arthritis). Experts, with precision, should perform this type of injections.

Intracerebral, Intracisternal, Intraventricular, Intraneural

            In this drugs are given in certain parts of the brain in rare conditions. These are surgical procedures.

Intravenous in young animals

            Drugs are injected through umbilical vein.

Sub conjunctival injection

            Used in corneal disorders.

Intramammary infusion

            Used for introduction of antiseptics in mastitis condition.

 

Special drug delivery systems: Drug delivery systems have become the much sought for research in Pharmacology. Some of the special drug delivery systems include biologically erodable microspheres, pro-drugs, antibody-drug conjugates and packaging in liposomes.

Biologically erodable microspheres: Microspheres of biologically erodable polymers can be engineered to adhere to mucosal epithelium in the gut. Such microspheres can be loaded with drugs, including high molecular weight substances as a means of improving absorption, which occurs through mucosal absorptive epithelium and also through epithelium overlying Payer's patches.

Pro-drugs: Pro-drugs are inactive precursors, which are metabolized to active metabolites. Some pro-drugs confer no obvious benefits while some have advantages. Cyclophosphamide an anticancer drug becomes active only after it undergoes metabolism in the liver and hence severe damage to the gastrointestinal epithelium can be avoided.

Antibody-drug conjugates: One of the aims of cancer chemotherapy is to improve the selectivity to cytotoxic drugs. One interesting possibility is to attach the drug to an antibody directed against tumour specific antigen, which will bind selectively to tumour cells.

Packaging in liposomes: Liposomes are minute vesicles produced by sonication of an aqueous suspension of certain phospholipids. They can be filled with non-lipid soluble drugs or nucleic acid sequences, which are retained until the liposome is disrupted. Liposomes are mainly taken up by the reticuloendothelial cells especially in the liver. They are also concentrated in the malignant tumour and there is a possibility of achieving selective delivery of drugs in this way.