Non-Nucleoside Reverse Transcriptase Inhibitors NNRTI
Non-nucleoside reverse transcriptase inhibitors are the smallest class of drugs used for Human Immunodeficiency Virus therapy. The class only contains three medications and all three are indicated for usage against HIV-1. The three medications are delavirdine (Rescriptor), nevirapine (Viramune) and efavirenz (Sustiva). In common ART practice, these drugs are never given alone but rather they are given in combination therapy.
Pharmacia and UpJohn Laboratories manufacture Delavirdine. The recommended dosage is 400mg three times a day and is available in 100mg tablets. Nevirapine is manufactured by a Boehering subsidiary, Roxane Labs, and is recommended at 200mg once daily for 14 days, then increase to 200mg twice daily. Nevirapine is available in 200mg tablets. Efavirenz is recommended at 600mg once daily and is available in 200mg, 100mg and 50mg capsules. It is made by DuPont Pharmaceuticals.
The assay methodology used in achieving PK information about delavirdine was obtained by taking serial plasma and urine collections over a 6 hour period. The samples were then flown to the University at Buffalo, specifically Gene Morse's lab, where the pharmacokinetics were determined by high pressure liquid chromatography (1). The pharmacokinetics of nevirapine were determined using HPLC and UV spectroscopy (2). The pharmacokinetics of efavirenz were also determined with plasma samples. The metabolites were obtained using HPLC with UV detection. The subsequent graphs were then compared against previously obtained UV samples of efavirenz (3).
The AUC of efavirenz increased with dose exponentially in monkeys and the average in humans was 57.15mcg/(ml)(hr) (4). In dela...
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...er, there were no active metabolites for any of the three medications. Nevirapine was metabolized to 2-hydroxynevirapine glucuronide (18.6%), 3-hydroxynevirapine glucuronide (25.7%) and 12-hydroxynevirapine glucuronide (23.7%). 80% of the excreted drug was made up of a glucuronidated compound (7). The major metabolite discovered from delavirdine is desalkyl delavirdine. Most of the Phase I metabolism of delavirdine involves hydroxylation while Phase II metabolism consists of glucuronidation, sulfation and beta-N-acetylglucosamination(10, 11). The major metabolite seen with efavirenz degradation was the O-glucuronide conjugate of the 8-hydroxylated metabolite. Efavirenz was mainly the subject of glucuronidation, much like the other two NNRTIs(3).
Overall, the NNRTIs are a very complex group of medications; despite they're only being 3 drugs in the class.
Human Immunodeficiency Virus (HIV) was once considered a taboo disease that made its appearance in the United States around the late 1970s. Little was known about the virus and it was originally thought to just be found in the gay male community. As more and more research has been done people now understand the virus and realize that it affects men and women as well as all races, ages, and sexual orientation. It is believed that HIV is a mutated form of the Simian Immunodeficiency Virus (SIV) that
The AIDS virus was a major turning point in world history. Contrary to popular belief, if a person gives blood to or recieves blood from a hospital or blood bank that person will not risk transmitting HIV, a.k.a. human immunodeficiency virus and that person does not risk transmitting AIDS, a.k.a. acquired immunodeficiency syndrome. In addition, “It is now generally accepted that HIV is a descendent of a Simian Immunodeficiency Virus because certain strains of SIVs bear a very close resemblance to
mortality and morbidity associated with HIV infection. However, even with the reduction in mortality and morbidity, there are still some adverse effects caused by these drugs. Hepatotoxicity is commonly seen in patients taking Non- Nucleoside Reverse Transcriptase Inhibitors (NNRTI), a drug used in HAART. Drug-induced liver injury is responsible for more than 50% of cases of acute liver injury in the United States. Furthermore, patients with concurrent Hepatit... ... middle of paper ... ... and micronodular