Tenofovir Disoproxil Fumarate (TDF, CAS 202138-50-9)
Meta Descriptions
Tenofovir Disoproxil Fumarate (TDF, CAS 202138-50-9) is a nucleotide reverse transcriptase inhibitor (NRTI) used for the treatment of HIV-1/2 infections and chronic hepatitis B. As a prodrug, it is hydrolyzed to tenofovir, which inhibits viral DNA polymerase by competing with natural deoxyribonucleotides, thereby terminating viral replication. Approved by the WHO as an essential medicine, TDF is widely prescribed in combination therapies such as Truvada® (TDF + emtricitabine) for HIV pre-exposure prophylaxis (PrEP).
替诺福韦二吡呋酯（TDF，CAS 202138-50-9）是一种核苷类逆转录酶抑制剂（NRTI），用于治疗HIV-1/2感染和慢性乙型肝炎。作为前药，其在体内水解为替诺福韦，通过竞争性抑制病毒DNA聚合酶阻断病毒复制。该药物被世界卫生组织列为基本药物，常与恩曲他滨联用（如Truvada®）用于HIV暴露前预防（PrEP）。
1. Basic Information
- Chemical Name: Tenofovir Disoproxil Fumarate (TDF)
- CAS Number: 202138-50-9
- Molecular Formula: C₂₃H₃₄N₅O₁₄P
- Molecular Weight: 635.52 g/mol
- Appearance: White to off-white film-coated tablets imprinted with “GSK” and “300”.
- 化学名称：替诺福韦二吡呋酯（TDF）
- CAS号：202138-50-9
- 分子式：C₂₃H₃₄N₅O₁₄P
- 分子量：635.52 g/mol
- 性状：白色至类白色薄膜衣片，刻有“GSK”和“300”标识。
2. Pharmacological Mechanism
- Mechanism of Action:
- TDF acts as a prodrug, converted to tenofovir via hydrolysis. Tenofovir is phosphorylated intracellularly to its active form, tenofovir diphosphate, which competitively inhibits HIV reverse transcriptase and HBV DNA polymerase, terminating viral DNA elongation.
- Effective against HIV-1 (EC₅₀ = 5.9 μM) and HIV-2 (EC₅₀ = 4.9 μM).
- Pharmacokinetics:
- Absorption: Peak plasma concentration reached 1–2 hours post-dose; bioavailability increased by 40% with food.
- Metabolism: Not metabolized by CYP450 enzymes; primarily excreted unchanged via kidneys (70–80%).
- Half-life: Plasma half-life ~17 hours; intracellular half-life >60 hours, supporting once-daily dosing.
- 作用机制：
- TDF为前药，水解后生成替诺福韦，后者在细胞内磷酸化为活性代谢物替诺福韦二磷酸，竞争性抑制HIV逆转录酶和HBV DNA聚合酶，终止病毒DNA链延伸。
- 对HIV-1（EC₅₀=5.9 μM）和HIV-2（EC₅₀=4.9 μM）均有效。
- 药代动力学：
- 吸收：口服后1–2小时达峰，食物使生物利用度增加40%。
- 代谢：不经CYP450酶代谢，主要经肾排泄（70–80%以原形排出）。
- 半衰期：血浆半衰期约17小时，细胞内半衰期>60小时，支持每日一次给药。
3. Clinical Applications
- Indications:
- HIV-1/2 Infection: Combined with other antiretrovirals for adults and children ≥12 years.
- Chronic Hepatitis B: For compensated liver disease in adults and children ≥12 years.
- Fixed-Dose Combinations:
- Truvada® (TDF + emtricitabine): Pre-exposure prophylaxis (PrEP) for HIV.
- Atripla® (TDF + emtricitabine + efavirenz): Once-daily single-tablet regimen.
- 适应症：
- HIV-1/2感染：联合其他抗逆转录病毒药物治疗成人及≥12岁儿童HIV感染。
- 慢性乙型肝炎：治疗成人及≥12岁代偿性肝病患者。
- 复方制剂：
- **Truvada®**（TDF + 恩曲他滨）：HIV暴露前预防（PrEP）。
- **Atripla®**（TDF + 恩曲他滨 + 依非韦伦）：每日一次单片疗法。
4. Dosage and Administration
- Adults: 300 mg once daily, with or without food.
- Renal Impairment: Dose adjustment required for CrCl <50 mL/min (e.g., extended dosing interval).
- Special Populations:
- Pregnancy: Risk-benefit assessment required; avoid combination therapies.
- Pediatrics: Approved for ≥12 years with weight ≥35 kg.
- 剂量：
- 成人：300 mg/日，空腹或随餐服用。
- 肾功能不全：肌酐清除率<50 mL/min时需调整剂量（如延长给药间隔）。
- 特殊人群：
- 孕妇：需医生评估风险与获益，避免与复方制剂联用。
- 儿童：≥12岁且体重≥35 kg可用。
5. Adverse Effects and Precautions
- Common: Diarrhea (19%), nausea, abdominal pain.
- Metabolic: Hypophosphatemia (1%), rare lactic acidosis (potentially fatal).
- Bone Toxicity: Long-term use may reduce bone mineral density.
- Hepatotoxicity: HBV treatment discontinuation may cause flare-ups; monitor liver function.
- Drug Interactions: Avoid concomitant use with didanosine (requires dose reduction); adjust atazanavir dosage.
- 常见不良反应：
- 胃肠道：腹泻（19%）、恶心、腹痛。
- 代谢：低磷血症（1%）、罕见乳酸酸中毒（可能致命）。
- 骨骼：长期使用可能导致骨密度下降。
- 严重风险：
- 肝毒性：HBV治疗中断可能引发恶化，需持续监测。
- 肾毒性：罕见范可尼综合征（肾小管损伤伴低磷血症）。
- 药物相互作用：
- 避免联用：含替诺福韦的复方制剂（如Truvada）。
- 慎用药物：去羟肌苷（需减量）、阿扎那韦（需调整剂量）。
6. Research and Developments
- Next-Generation Drugs: Tenofovir Alafenamide (TAF, 25 mg dose) offers reduced renal and bone toxicity, preferred for long-term PrEP.
- Prevention:
- PrEP: Reduces HIV infection risk by 48.9% in high-risk populations (e.g., people who inject drugs).
- Transgender Youth: Pharmacokinetic data show safety comparable to cisgender populations.
- 替代药物：
- 替诺福韦艾拉酚胺（TAF）：剂量更低（25 mg），肾毒性和骨代谢影响更小，适用于长期PrEP。
- 预防应用：
- PrEP：降低高危人群HIV感染风险达48.9%。
- 跨性别青少年：药代动力学显示安全性良好。
7. Market and Regulatory Status
- Global Approval: Approved in 2001; listed in WHO Model List of Essential Medicines.
- China: Included in National Reimbursement Drug List (March 2025), priced at ¥460–510 per 300 mg tablet.
- 上市情况：2001年首次获批，列入WHO基本药物清单。
- 中国获批：2025年3月纳入医保乙类，规格300 mg，价格460-510元。
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