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Current Status of the Pharmacokinetics and Pharmacodynamics of HIV-1 Entry Inhibitors and HIV Therapy

Current Status of the Pharmacokinetics and Pharmacodynamics of HIV-1 Entry Inhibitors and HIV Therapy

Fengyan Xu, Edward P Acosta, Liyu Liang, Yingchun He, Juan Yang, Corenna Kerstner-Wood, Qingshang Zheng, Jihan Huang, Kun Wang

Curr Drug Metab. 2017 Oct 16;18(8):769-781.

PMID: 28738768

Abstract:

Background:
Human Immunodeficiency Virus (HIV) entry inhibitors target the first step of the HIV life cycle and efficiently inhibit HIV from infecting the immune cells which is a key prerequisite for viral spread. Because of their unique mechanism of action on cell-cell transmission, they may provide a promising perspective for the treatment of AIDS.
Method:
Maraviroc (MVC) and Enfuvirtide (ENF) have been approved by the FDA for the treatment of HIV-1 infection. Attachment inhibitors (BMS-663068 and TNX-355) and co-receptor inhibitors (PRO-140 and cenicriviroc (CVC)) have reached phase II or III clinical trials. These entry inhibitors show beneficial pharmacokinetics and substantial reductions of plasma HIV-1 RNA load in HIV infected patients.
Results:
Most entry inhibitors are generally safe, without serious Adverse Event (AE) or AE leading to discontinuation. The pharmacokinetics of MVC, CVC and BMS-663068 was affected by CYP3A4 inhibitors or inducers. The FDA has proposed that the dosage of MVC (300 mg, BID, orally) be adjusted to half or two-fold for patients if it is combined with a major CYP3A4 inhibitor or inducer, respectively. Researchers suggested that the dosage of CVC (50-75 mg, QD, orally) may also need adjustment but the dosage of BMS-663068 (600 mg, BID, orally) does not.
Conclusion:
The standard, recommended ENF dosage is 90 mg BID, injected subcutaneously for adults, and 2 mg/kg BID, up to a maximum dose of 90 mg, injected subcutaneously for pediatric patients. TNX-355 (10-15 mg/kg, BID, intravenously) and PRO-140(5-10 mg/kg, BID, intravenously; 324 mg, biweekly, subcutaneously) are administered by intravenous infusion or subcutaneous injection.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42412570	BID human			Price

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