化合物详情

Although it is not known whether amprenavir is distributed in human milk, the drug is distributed into milk in rats.

If overdosage occurs, the patient should be monitored for evidence of toxicity and standard supportive treatment applied as necessary. (L1712)

Although antacids have not been specifically studied with amprenavir, based on data from other protease inhibitors, antacids (and didanosine due to the antacid content present in didanosine formulations) may interfere with the absorption of amprenavir; it is recommended that antacid and didanosine administration be separated from amprenavir administration by at least one hour.

Rapidly absorbed after oral administration in HIV-1-infected patients with a time to peak concentration (T_max) typically between 1 and 2 hours after a single oral dose. The absolute oral bioavailability of amprenavir in humans has not been established.

Amprenavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.

/HUMAN EXPOSURE STUDIES/ Although these medications /astemizole, bepridil, cisapride, dihydroergotamine, ergotamine, midazolam, or triazolam/ have not been specifically studied with amprenavir, amprenavir may interfere in the metabolism of these medications and cause serious or life threatening adverse events; concurrent use is not recommended.

No indication of carcinogenicity to humans (not listed by IARC).

References: DOI:10.1016/j.drudis.2016.02.015

/GENOTOXICITY/ Amprenavir was not mutagenic or genotoxic in several in vitro and in vivo assays, including bacterial mutation, mouse lymphoma, rat micronucleus, and chromosomal aberration assays in human peripheral blood lymphocytes.

The usually recommended dosage of amprenavir oral solution (22.5 mg/kg twice daily) provides a propylene glycol intake of 1650 mg/kg daily; however, an acceptable intake of propylene glycol used as an excipient in pharmaceuticals has not been established to date. Propylene glycol is metabolized in the liver by the alcohol and aldehyde dehydrogenase enzyme pathway, and the possibility exists that young infants, patients with renal or hepatic impairment, and certain patient groups (females, Asians, Native Alaskans, Native Americans) may be at increased risk of propylene glycol-associated adverse effects if they receive amprenavir oral solution because of diminished ability to metabolize propylene glycol /SRP: due to alcohol dehydrogenase polymorphism/.

Maintain an open airway and assist ventilation if needed. Treat coma, seizures, hypotension or anaphylaxis if they occur. replace fluid losses resulting from gastroenteritis with intravenous crystalloids. Maintain steady urine flow with intravenous fluids to alleviate crystalluria and reverse renal dysfunction. Treat lactic acidosis with judicious doses of sodium bicarbonate and by withdrawal of the offending drug. There are no specific antidotes for these agents. Administer activated charcoal.