Нелфинавир

Использование

Antiviral.

Определение

ChEBI: An aryl sulfide that is used (as its mesylate salt) for treatment of HIV and also exhibits some anticancer properties.

Показания

Nelfinavir (Viracept) is probably the most commonly used protease inhibitor because of its low incidence of serious adverse effects. Its most common side effects are diarrhea and flatulence; these may resolve with continued use. In addition to the drugs contraindicated for use with all protease inhibitors, amiodarone, rifampin, and quinidine are contraindicated in patients taking nelfinavir.

Антимикробная активность

Nelfinavir inhibits HIV-1 and HIV-2 proteases. Bioavailability is affected to only a limited degree by combination with lowdose ritonavir.

Приобретенная устойчивость

Resistance is most frequently selected through a D30N mutation in the HIV protease. An L90M mutation also confers resistance.

Фармацевтические приложения

A synthetic chemical formulated as the mesylate for oral administration.

Фармакокине?тика

Oral absorption: c. 70–80% (with food)
C_max 750 mg thrice daily: c. 3–4 mg/L
1250 mg twice daily: c. 4 mg/L
C_min 750 mg thrice daily: c. 1–3 mg/L
1250 mg twice daily: c. 0.7–2.2 mg/L
Plasma half-life: c. 3.5 h
Volume of distribution: c. 2–7 L/kg
Plasma protein binding: >98%
Absorption and distribution
Food improves the bioavailability and the drug should be administered with a light meal. The semen:plasma ratio is 0.07. It is distributed into breast milk.
Metabolism and excretion
One major and several minor oxidative metabolites are found in plasma. Most of an oral dose is recovered in feces as unchanged drug (22%) and metabolites (78%). The remainder is recovered in urine, mainly unchanged.
An increase in the area under the time–concentration curve (AUC) has been observed in patients with hepatic impairment, but specific dose recommendations have not been made.

Клиническое использование

Treatment of HIV infection (in combination with other antiretroviral drugs)

Побочные эффекты

The most common adverse effect is diarrhea of mild to moderate severity. Other side effects include nausea, fatigue, vomiting and headache. It is associated with less dyslipidemia in comparison with ritonavir-boosted protease inhibitors.

Метаболизм

Following oral administration, nelfinavir peak levels in plasma ranged from 0.34 mg/mL (10 mg/kg in the dog) to 1.7 mg/mL (50 mg/kg in the rat). In the dog, nelfinavir was slowly absorbed, and bioavailability was 47%. The drug appeared to be metabolized in the liver, and the major excretory route was in feces.