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In this experiment, there are five different routes of administration are used to these mice to know the onset

of the drug to produce response. Pentobarbital sodium (Nembutal) 35mg/kg (0.1ml/10 gm) is applied to the subject, mice. The common routes of administration that are used are oral administration, subcutaneous injection, intravenous injection, intraperitoneal injection and intramuscular injection. Some substances may be effective when administered by one route but it may be not effective and do not produce response required when given by another. The mode of entry of a drug into body determines the speed, dose and degree of action. There are 10 mice are used to conduct this experiment. Each route of administration used two mice. Before the experiment is started, the mice are marked from mouse 1 until mouse 10 to prevent interchange of the mouse and to see the response of drug for each of these mice that are given different route of administrations of drug. Before the drug is given to each mouse, each mouse is weighed to determine the correct doses of the drug required for each mouse based on the weight. Firstly, oral administration of drug is the most common routes in administrating drugs. It is suitable for the drug that is the most convenient, safe and easily administered. However, taking drug by orally, it gives the lowest bioavailability compared to intravenous and subcutaneous injection. It takes the longest time to produce drug response. This is due to incomplete absorption and first-pass metabolism that occur in gastrointestinal tract (GIT). Most of the drug that are taken orally undergo first-pass metabolism effect, the drug absorbed from the GIT enter the circulation and passes through liver. In the liver, the drug meets enzymes able to metabolise it and transform it into one or more metabolites, some of them are active but generally inactive. Then, it will enter systemic circulation to the target organ or tissue to produce the desired effect and some of them will be excreted into the kidney and will be eliminated. Due to this reasons, it takes longer time to produce therapeutic effects. The first-pass metabolism drug will determine the bioavailibilty of the drug. Some drug may be destroyed by the acidic condition in the stomach and thus, this will affect bioavailability of drug due to less absorption of drug in the intestine membrane. Therefore, other methods should be applied such as by taking capsules, sugar-coated or film-coated drug. This will delay the release of drug in the stomach so that, it will not be destroyed by gastric juices, stomach lining will be protected by irritating effect of drug when the drug is taken orally. This will take longer time to produce desired effect due to the delay effect of the drug in the stomach.

There are some factors that can influence absorption of drug when it is taken orally. Firstly, solubility of the drug affects absorption of the drug. Higher solubility of the drug will be absorbed easily. Secondly, permeability of the drug is the ability of drug to permeate the intestinal membranes due to charge, degree of ionization, partition coefficient and lipophilicity of drug. Unionized formed of the drug will be easily permeate across membrane. Moreover, hydrophilic drug (polar) are unable to across the membrane. Lastly, chemical stability of the drug affects the absorption of the drug. If the drug is unstable, it will be break down and then, it will be excreted. Secondly, subcutaneous injection is aqueous solutions or suspensions which allow drug to be place in the immediate vicinity of blood capillaries (fatty layer of tissue under the skin). The drug will then diffuse into capillaries. It produces effect faster than oral administration but the rate of absorption depend on the site of injection and local blood flow. Absorption from a site of injection increases as the blood flow increases. Through subcutaneous injection, the drug should be diffused into the capillaries of blood vessels from the fatty layer of tissue under the skin. Due to this reason, it is slower and takes longer time to produce response compared to intravenous injection. Thirdly, intravenous injection (IV) administration involve INTRAVENOUS INJECTION Theoretically, intravenous (IV) administration will have the shortest time of onset and duration of action as intravenous delivery allows rapid action of the drug and provides 100% bioavalaibility. This is due to the fact that through IV administration, the drug is directly delivered into the vein and does not pass through GI tract or undergo first-pass metabolism by the liver. However, from the experiment conducted, the time of onset and duration for the IV administration is not the fastest among the other routes as intraperitoneal and intramuscular injections recorded shorter time of onset compared to it. This might due to errors occurred when administrating or injecting the drug into the mice or mistakes when recording the time of onset and duration of action. Theoretically, intravenous administration gives highest efficacy followed by intramuscular, intraperitoneal, subcutaneous, and oral administration. Intravenous injection (IV) injection is the most common parenteral route. For drug that are not absorbed orally, there is often no other choice. With IV administration, the drug avoids avoids the GI tract and therefore, first-pass metabolism by the liver. Intravenous delivery permits a rapid effect and a maximal degree of control over the circulating levels of the drug. However, unlike drugs in the GI tract, those that are injected cannot be recalled by strategies such as emesis or by binding to activated charcoal. Intravenous injection may inadvertently introduce bacteria through contamination at the site of injection. IV injection may also induce hemolysis or cause other adverse reactions by the too-rapid delivery of high concentrations of drug to the plasma and tissues. Therefore, the rate of infusion must be carefully controlled.

Drugs administered IM can be aqueous solutions or specialized depot preparations, often a suspension of drug in a nonaqueous vehicle. Absorption of drugs in an aqueous solution is fast, whereas that from depot preparations is slow. As the vehicle diffuses out of the muscle, the drug precipitates at the site of injection. The drug then dissolves slowly, providing a sustained dose over an extended period of time. In conducting this experiment, several precautions have been taken into consideration in order to avoid the errors. First, the mouse was held at the middle part of it tail. If it was held at the distal, the mouse would be easily fallen down; in contrast, it would bite the experimenter if it was held at the proximal end of the tail. Second, the mice should be in normal condition. The experimenter should familiarize herself with the mice so that they would be in calm situation. Nervous condition will affect the absorption of the drug that will further affect the onset and duration period. Third, the onset and duration should be well observed. Once the drug being administered, the onset began. The duration period began when immobility and righting was not attempted. There were several errors occurred through out this experiment. The onset and duration period was not well observed as the experimenters could not assume the exact situation of immobility of the mouse for oral administration. Besides, the dose of the drug was reduced as Nembutal was not fully injected into the mouse. Nervous situation of the mice might also affected the absorption and metabolism of the drug. The different in gender of mice might also affect the results. This is because female mice are more susceptible to drugs like pentobarbital than male mice. INTRAVENOUS INJECTION Theoretically, intravenous (IV) administration will have the shortest time of onset and duration of action as intravenous delivery allows rapid action of the drug and provides 100% bioavalaibility. This is due to the fact that through IV administration, the drug is directly delivered into the vein and does not pass through GI tract or undergo first-pass metabolism by the liver. However, from the experiment conducted, the time of onset and duration for the IV administration is not the fastest among the other routes as intraperitoneal and intramuscular injections recorded shorter time of onset compared to it. This might due to errors occurred when administrating or injecting the drug into the mice or mistakes when recording the time of onset and duration of action. INTRAPERITONEAL INJECTION Intraperitoneal injection is a common method of introducing drugs into animals. The drug is injected into the peritoneal cavity and from there the drug will enter the blood circulation. The time of onset and duration for this route of administration is said to be faster that subcutaneous but slower than intramuscular. INTRAMUSCULAR INJECTION In intramuscular injection, the drug is inserted into the gluteus maximus muscle of the mouse and from the muscle, the drug is released slowly into the blood vessels which supply the muscle and distributed to other parts of body. Intramuscular route provides a faster rate of absorption than the subcutaneous route. Besides that, muscle tissues can hold a large volume of fluid without discomfort. Nevertheless, the time of onset for intramuscular injection is slower than of intravenous as the drug must undergo absorption process from the muscle tissue before it is available in the blood circulation.

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