Safety and Tolerability Of Abacavir

The tolerability and safety of abacavir has been tested taking into consideration the measurements and reports on the alterations of the vital signs of the subjects that are under study. The routine hematological tests have also been done to ensure that the bioavailability of the drugs is accurately recorded before the drug is taken into the market (Guideline, 2000). The potency of the of the drug, abacavir has been tested alongside other nucleoside transcriptase inhibitors like zidovudine and lamivudine to test whether it is safe to be used on the patients especially the infants. The previous conditions of the targeted patients had been determined before the drug under study was administered to them (Podany et al, 2017). According to the centers of evaluation and drug research, abacavir was brought on board in 1st June 1994 where it was tested for safety.

The drug was then approved to be safe in 24th June on the same year. Abacavir is a nucleoside reverse transcriptase inhibitor that exhibits selectivity against the HIV type 1 (Yuen et al 2008). The drug has been recorded to give favorable safety profiles on organisms that are used for tests including the monkeys and mice. A study has been done to determine the pharmacokinetics and safety profile of Abacavir on the infants to determine whether it can be used to other humans for the treatment of humans. The tests were done on determinable number of patients who were majority infants (Alexander et al 2013). The drug progressions were checked within the intervals of thirty minutes and the final check up for the drug progression (Golan et al 2008). The effects of the abacavir administration were checked using the chromatography films.

The information that was found from the chromatography records were determined using various techniques to ensure that the slightest abnormality that arises from the drug does not go unnoticed. The drug was determined to be well tolerated by most individuals. The side effects that resulted from the drugs that were expressed by a low percentage of the infants included rash. Determination of the drug safety plays a major impact in the determination of the success of the drug. The toxicity of the drug may test in various categories including the regulatory toxicology and the exploratory toxicology among others. Abacavir was taken through the various stages of the exploratory toxicology whereby the drug was tested on various species of mice and monkeys (Himes et al 2013). The dosage was determined through repeated dosages of groups of 100mg per kg for the determination of the side effects that are related to the drug.

The side effects of the drug was also determined for considerably long time periods and it was determined that the side effects of the drugs may result from hypersensitity reactions of the body. The side effects can be noticed in a time span of between one to three months. The main side effect of the drug to the liver is the increase in the level of the serum aminotransferase in the body. The increase in the aminotransferase levels occurs in a very small percentage of the test animals and this reflects that the drug affects individuals with certain genotype.

The abacavir hypersensitivity syndrome has also been determined to the major factor that results in the liver damage as a result of the use of the drug. Abacavir is said to have a relatively low molecular weight of about 281.4 with sodium sulfate as one of its composition. The drug is weakly basic. It is among the nucleoside reverse transcriptase inhibitors that have the great capability of crossing the blood brain barrier. In the mice and the monkeys, the drug has been found to be related to low instances of the mutations and cytotoxicity if not taken with other drugs that have great impacts on its clearance.

The drug is sometimes related to the neurophysiologic deterioration. Renal deterioration and cardiac deterioration are some of the side effects that come with the use of the drug. In the regulatory studies on abacavir, the drug was administered in mice for more than three months and the main side effects that resulted are those that can be noticed within the three months duration. In some mice, the drug had been determined to cause myocardial degeneration. In close examination of the main factor that might be the cause of the serious side effects that are associated with the use of the drug, it was determined that the side effects are related to the HLA-B*57:01 allele (Bachelerie et al 2013). The individuals having the HLA-B*57:01 allele need to be taken within caution when a practitioner needs to prescribe the drug to them because the side effects involved are quite adverse.

The drug has also been noted to have interactions with other drugs. In case of alcohol intake, the clearing of the drug is said to have been greatly reduced. The clearance of the drug is said to be improved by the presence of methadone. Individuals who are taking methadone regiments should have different prescription from those who are not talking methadone because of the differences that come with the drug interactions. In another instance, the safety of the drug was tested on naïve individuals as monotherapy or in combination with other drugs like zidovudine. The drug performance was monitored against the changes that occur in the CD4+ counts.

The test for the drug was done for a period of twelve weeks in various classifications of patients. The patients, CD4+ counts were noted to improve with the administration of abacavir and this indicates that the drug is highly potent in the regulation of adversity of HIV (Piana 2013). In infants, the drug is preferred as a monotherapy while in adults; the drug is used in combination with other drugs. The drug has been recorded to express very low possibilities of cytotoxicity.

On its pharmacokinetics, abacavir is administered orally. The drug is well absorbed in the gut if its bioavailability of about eighty three percent is to go by. The drug has lipophilic characteristic and also expresses with good solubility in water. These characteristics give the drug credit concerning its absorption through the walls of the stomach. The properties of the drug enable it pass through the walls of the stomach by passive diffusion alone. The properties of the drug give a clear explanation why the drug has a high bioavailability and why it easily reaches the brain through the blood brain barriers. Abacavir is metabolized extensively in the liver (Bouazza et al 2013). Very low composition of abacavir is determined in patients who chose to take abacavir as their medication. The composition of abacavir that may be found unchanged in urine is found to be less than two percent.

The metabolism of the abacavir is aided by special enzymes that are present in the hepatocytes. The enzymes involve the UGT and the ADH (Schoen et al 2016). The metabolism by of the drug by UGT results in the carboxylate metabolite. It has been found that majority of the end product of the drug (83%) is found in the urine while the remaining percentage is excreted through the fecal matter. Of the eighty three percent that is excreted through urine, about thirty percent is the carboxylate metabolite that results from metabolism by ADH (Burke et al 2016). UGT metabolism results into the formation of glucuronide metabolite that occupies about thirty percent of the eighty three percent that is excreted through urine. The remaining percentage of the eighty three is believed to be composed of the parent drug.

The parent abacavir drug that has not undergone metabolism in the hepatocytes normally undergoes anabolism for it to be converted to its active metabolite. The process of the anabolism of the parent form of the drug is initiated by the enzyme called adenosine phosphotransferase (Singh 2016). The drug is converted to abacavir 5- monophosphate. The drug then go through a deamination process by unknown enzymes that are normally present in the cytoplasm to ensure that is converted to the carbovir 5 monophosphate form. Phosphate group is again added to the carbovir 5 monophosphate to form carbovir 5 diphosphate. The addition of the phosphate group is taken care of by the guanylate kinase (Turner 2013).

The guanylate kinase is said to be enantiomer specific. The guanylate kinase is specific to the (-) enantiomer of the carbovir 5 monophosphate. The preference of the enzyme to the negative enantiomer has been determined to be more than seven thousand times that of the positive enantiomer. The carbovir 5 diphosphate is then converted to the active 5 triphosphate by various enzyme that are present in the cytoplasm including the pyruvate kinase and the creatine kinase. In other instances, the parent drug is normally converted through other means to meet the target impacts in the body. The half life of abacavir is about one and a half hours.

300mg is normally administered orally after every day (Huestis et al 2013). The administration of the 300mg twice daily has been noted to cause no accumulation in the body and thus marks the appropriate dosage for the children who are exposed to HIV at infancy. The administration of the drug orally has been determined in both solution and tablet forms (Zhao et al 2013). Though the two have similar impacts, the tablet forms have been recorded to cause a greater plasma concentration that the suspension forms. Admission of abacavir to infants over three months has been contraindicated.

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