أباكاڤير
أباكافير أباكافير Abacavir (ABC) هو nucleoside مشتق reverse transcriptase inhibitor NRTI) يستعمل لعلاج HIV and AIDS. وهو متوافر بأسماء تجارية Ziagen (GlaxoSmithKline) وبتركيبات Trizivir (abacavir, zidovudine و lamivudine)
 Chemical structure of abacavir | |
| البيانات السريرية | |
|---|---|
| فئة السلامة أثناء الحمل |
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| مسارات الدواء | Oral (solution or tablets) |
| رمز ATC | |
| الحالة القانونية | |
| الحالة القانونية |
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| بيانات الحركية الدوائية | |
| التوافر الحيوي | 83% |
| الأيض | Hepatic |
| Elimination half-life | 1.54 ± 0.63 hours |
| الإخراج | Renal (1.2% abacavir, 30% 5'-carboxylic acid metabolite, 36% 5'-glucuronide metabolite, 15% unidentified minor metabolites). Fecal (16%) |
| المعرفات | |
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| رقم CAS | |
| PubChem CID | |
| DrugBank | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.149.341  |
| Chemical and physical data | |
| التركيب | C14H18N6O |
| الكتلة المولية | 286.332 g/mol |
| 3D model (JSmol) | |
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وKivexa/Epzicom(abacavir و lamivudine) . والجسم يتحمله جيدا: أهم آثاره الجانبيةhypersensitivity, التى يمكن أن تكون شديدة, وفى أحيان نادرة مميتة. الإختبارات الوراثية يمكن أن تظهر ما إذا كان الشخص سيكون حساسا; ونسبة فوق 90% من المرضى يكنهم إستعمال الدواء بدون محاذير. وفى دراسة منفصلة فإن مخاطر أزمات قلبية قد إزدادت. [1]
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Viral strains that are resistant to zidovudine (AZT) or lamivudine (3TC) are generally sensitive to abacavir, whereas strains that are resistant to AZT and 3TC are not as sensitive to abacavir.
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التاريخ
Abacavir was approved by the Food and Drug Administration (FDA) on December 18, 1998 and is thus the fifteenth approved antiretroviral drug in the United States. Its patent will expire in the United States on 2009-12-26.
الإستعمالات
Abacavir tablets and oral solution, in combination with other antiretroviral agents, are indicated for the treatment of HIV-1 infection.
Abacavir should always be used in combination with other antiretroviral agents. Abacavir should not be added as a single agent when antiretroviral regimens are changed due to loss of virologic response.
نظرية العمل
ABC is an analog of guanosine (a purine). Its target is the viral reverse transcriptase enzyme.
الحراك الدوائى
Abacavir is given orally and has a high bioavailability (83%). It is metabolised primarily through alcohol dehydrogenase or gluconyl transferase. It is capable of crossing the blood-brain barrier.
الآثار الجانبية
Fatal hypersensitivity reactions have been associated with therapy with abacavir. Symptoms of hypersensitivity include fever, skin rash, fatigue, gastrointestinal symptoms such as nausea, vomiting, diarrhea or abdominal pain and respiratory symptoms such as pharyngitis, dyspnea, or cough. Hypersensitivity is strongly associated with HLA-B*5701[2][3] for which testing is now available in most western countries. There is a strong relationship with race: the prevalence of HLA-B*5701 in India is 20–50%, but is 0% in Japan; the prevalence is 5–7% in western Europe. Screening for the HLA-B*5701 has been convincingly shown to reduce the incidence of abacavir hypersensitivity reactions.[4][5]
A new FDA alert concerning abacavir and abacavir containing medications was issued on July 24, 2008. FDA informed that based on data from two studies they support a recommendation for pre-therapy screening for the presence of the HLA-B*5701 allele and the selection of alternative therapy in positive subjects. Genetic tests for HLA-B*5701 are available and all patients should be screened for the HLA-B*5701 allele before starting or restarting treatment with abacavir or abacavir containing medications. Development of clinically suspected abacavir HSR requires immediate and permanent discontinuation of abacavir therapy in all patients, including patients negative for HLA-B*5701.[6]
Cautions and Warnings
Patients with liver disease should be cautious about using abacavir because of the possibility that it can aggravate the condition.
The use of nucleoside drugs such as abacavir can very rarely cause lactic acidosis.
Resistance to abacavir has developed in laboratory versions of HIV which are also resistant to other HIV-specific antiretrovirals such as lamivudine, didanosine and zalcitabine. HIV strains that are resistant to protease inhibitors are not likely to be resistant to abacavir.
Redistribution or accumulation of body fat may occur in people taking antiviral medications giving rise to central obesity, facial arm, leg, and/ or buttock wasting, breast enlargement, and fat accumulation at the base of the neck (buffalo hump).
Abacavir is contraindicated for use in infants under 3 months of age.
التفاعل مع الأغذية
None known
الجرعة المعتادة
Adult (age 17 and over) :300mg 2 times a day Child (age 3 months - 16 years) 3.6mg per lb. of body weight twice a day, up to a maximum of 300mg in each dose.
زيادة الجرعة
Little is known about the effects of Abacavir overdose. Overdose victims should be taken to a hospital emergency room for treatment. Always bring the prescription bottle or container.
المراجع
- Antiretroviral Therapy-Investigational NRTIs: HIV Clinical Management Vol. 3. Medscape Inc, 1998
- HIV Insite Antiretroviral Drug Database; UC Regents, 1999
- ^ SFGate.com
- ^ Mallal S, Nolan D, Witt C; et al. (2002). "Association between the presence of HLA-B*5701, HLA-DR7 and HLA-DQ3 and hypersensitivity to HIV-1 reverse transcriptase inhibitor abacavir". Lancet. 359: 727–32. doi:10.1016/S0140-6736(02)07873-X.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Hetherington S, Hughes AR, Mosteller M; et al. (2002). "Genetic variations in HLA-B region and hypersensitivity reactions to abacavir". Lancet. 359: 1121–2. doi:10.1016/S0140-6736(02)08158-8.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Rauch A, Nolan D, Martin A; et al. (2006). "Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study". Clin Infect Dis. 43 (1): 99–102. doi:10.1086/504874.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Zucman D, de Truchis P, Majerholc C; et al. (2007). "Prospective Screening for Human Leukocyte Antigen-B*5701 Avoids Abacavir Hypersensitivity Reaction in the Ethnically Mixed French HIV Population". J Acquir Immune Defic Syndr. 45: 1. doi:10.1097/QAI.0b013e318046ea31. PMID 17356469.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ http://www.fda.gov/cder/drug/InfoSheets/HCP/abacavirHCP.htm FDA abacavir alert web access July 29, 2008