ネルフィナビル, FREE BASE 化学特性,用途語,生産方法
効能
抗ウイルス薬, HIVプロテアーゼ阻害薬
使用
Antiviral.
定義
ChEBI: An aryl sulfide that is used (as its mesylate salt) for treatment of HIV and also exhibits some anticancer properties.
適応症
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.
抗菌性
Nelfinavir inhibits HIV-1 and HIV-2 proteases. Bioavailability
is affected to only a limited degree by combination with lowdose
ritonavir.
獲得抵抗性
Resistance is most frequently selected through a D30N mutation
in the HIV protease. An L90M mutation also confers
resistance.
応用例（製薬）
A synthetic chemical formulated as the mesylate for oral
administration.
薬物動態学
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.
臨床応用
Treatment of HIV infection (in combination with other antiretroviral drugs)
副作用
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.
代謝
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.
ネルフィナビル, FREE BASE 上流と下流の製品情報
原材料
準備製品