エムトリシタビン

外観

白色～うすい黄色粉末～結晶

効能

抗ウイルス薬, 逆転写酵素阻害薬

商品名

エムトリバ (日本たばこ産業)

化学的特性

White to Off-White Crystalline Solid

使用

Labeled Emtricitabine, intended for use as an internal standard for the quantification of Emtricitabine by GC- or LC-mass spectrometry.

定義

ChEBI: An organofluorine compound that is 5-fluorocytosine substituted at the 1 position by a 2-(hydroxymethyl)-1,3-oxathiolan-5-yl group (2R,5S configuration). It is used in combination therapy for the treatment of HIV-1 infect on.

獲得抵抗性

Resistance is associated with a substitution in the HIV-1 reverse transcriptase gene at codon 184 (M184V/I). Emtricitabineresistant isolates are cross-resistant to lamivudine. HIV-1 isolates with the K65R substitution in the reverse transcriptase coding region have reduced susceptibility.

一般的な説明

Emtricitabine is an orally active NRTI whose pharmacokineticsare favorable for once-daily administration.

応用例（製薬）

A synthetic nucleoside analog of cytosine, formulated for oral use.

薬物動態学

Oral absorption: capsules 93%
C_max 200 mg oral once daily: 1.8 ± 0.7 mg/L
Plasma half-life: c. 10 h
Volume of distribution: 1.4 ± 0.3 L/kg
Plasma protein binding: <4%
Absorption and distribution
It is rapidly and extensively absorbed. There is moderate CNS penetration. The estimated semen:plasma ratio is approximately 4. There are presently no data on levels in breast milk.
Metabolism and excretion
It does not inhibit human cytochrome P₄₅₀ enzymes. About 80% is excreted in the urine, the rest in feces. Renal clearance is greater than the estimated creatinine clearance, suggesting elimination by both glomerular filtration and active tubular secretion. There may be competition for elimination with other compounds that are renally excreted. Exposure is significantly increased in renal insufficiency, but dose reductions are not generally recommended. It is unlikely that a dose adjustment would be required in the presence of hepatic impairment.

臨床応用

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

副作用

At least 10% of patients suffer headache, diarrhea, nausea, fatigue, dizziness, depression, insomnia, abnormal dreams, rash, abdominal pain, asthenia, increased cough and rhinitis. Skin hyperpigmentation is common (≥10%) in pediatric patients. Emtricitabine competes with lamivudine for the enzymes involved in intracellular phosphorylation; their co- administration is contraindicated.