인디나빌

인디나빌 속성

인디나빌 C화학적 특성, 용도, 생산

개요

Crixivan was launched in Australia, Switzerland, the UK and the US as an orally-bioavailable HIV-1 protease inhibitor. The compound can be prepared by coupling an optically active piperazine derivative with an epoxide derivative (now commercially available). The synthesis of the proteins, reverse transcriptase, integrase, structural proteins and a protease, required by the virus to complete its lifecycle, can be interupted if the protease enzyme is not capable of cleaving a proform polypeptide chain into these components. lndinavir inhibits this process and is more potent than the first approved protease inhibitor saquinavir. This effect was noted by the increase in CD4⁺ cells and a decrease in HIV RNA levels. Since indinavir is metabolized by the CYP3A4 isozyme, care must be taken with patients with hepatic insufficiency and to sex-related differences in the level of this enzyme. Other than nephrolithiasis (5%), indinavir is relatively safe and well tolerated.

Indications

Indinavir (Crixivan) is a potent inhibitor of HIV reverse transcriptase. It produces the side effects common to all protease inhibitors and also may produce nephrolithiasis, urolithiasis, and possibly renal insufficiency or renal failure. This problem occurs more frequently in children (approximately 30%) than adults (approximately 10%) and can be minimized by drinking at least 1.5 L of water daily. Additional side effects include asymptomatic hyperbilirubinemia, alopecia, ingrown toenails, and paronychia. Hemolytic anemia rarely occurs. Rifampin should not be given with indinavir.

원료

The major mutations in the protease enzyme associated with loss of the antiretroviral activity occur at positions 46, 82 and 84. Generally, the level of resistance rises with the number of point mutations.

일반 설명

When administered with a high-fat diet, indinavir(Crixivan) achieves a maximum serum concentration of77% of the administered dose. The drug is 60% bound inthe plasma. It is extensively metabolized by CYP3A4, andseven metabolites have been identified. Oral bioavailabilityis good, with a t_max of 0.8±0.3 hour. The half-life ofelimination is 1.8 hour, and the elimination products aredetectable in feces and urine. Indinavir also causes dyslipidemia.The available dosage forms are capsules of 200 mg,333 mg, and 400 mg.

Pharmaceutical Applications

A synthetic compound formulated as the sulfate for oral administration.

Pharmacokinetics

Oral absorption: c. 65%v C_max 800 mg thrice daily: c. 8.97 mg/L
C_min 800 mg thrice daily: c. 0.15 mg/L
Plasma half-life: c. 2 h
Volume of distribution: c. 0.4–1.74 L/kg
Plasma protein binding: c. 60%
Absorption and distribution
It is rapidly absorbed and not significantly affected by intake with food. Distribution in the body has not been fully characterized. It penetrates well into the CNS. The semen:plasma ratio is 1.9. It is distributed into breast milk.
Metabolism and excretion
Seven major metabolites have been described, including a glucuronide conjugate and six oxidative metabolites. Around 83% of the dose is recovered in feces and 18% in urine, 10% as unchanged drug. The effect of renal impairment has not been studied. It should be used with caution in the presence of hepatic impairment, particularly if severe.

Clinical Use

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

부작용

The principal side effect is nephrolithiasis, including flank pain with or without hematuria. There is good evidence that indinavir directly causes nephrolithiasis as a result of crystallization in the urinary tract. Indirect hyperbilirubinemia occurs in about 10% of patients associated with inhibition of bilirubinconjugating activity occurring as a result of competitive inhibition of uridine diphosphate (UDP)-glucuronosyltransferase.
Ritonavir-boosted indinavir is associated with a dyslipidemia profile characteristic of those treated with other protease inhibitors boosted with a 200 mg dose of ritonavir per day. Insulin resistance and hyperglycemia have also been associated with ritonavir-boosted indinavir.

신진 대사

The usual oral dose for indinavir alone or in combination with other antiviral agents is one 800 mg capsule every 8 hours. The drug is well absorbed if given on an empty stomach or 1 hour before or 2 hours after a light meal with water. The dose is reduced to 600 mg every 8 hours if given concurrently with ketoconazole. Indinavir activity is increased when combined with RT inhibitors.

인디나빌 준비 용품 및 원자재

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준비 용품

인디나빌 공급 업체

공급자	전화	이메일	국가	제품 수	이점
career henan chemical co	+86-0371-86658258	sales@coreychem.com	China	29914	58
Biochempartner	0086-13720134139	candy@biochempartner.com	CHINA	967	58
Chongqing Chemdad Co., Ltd	+86-023-61398051 +8613650506873	sales@chemdad.com	China	39916	58
CONIER CHEM AND PHARMA LIMITED	+8618523575427	sales@conier.com	China	47465	58
Shaanxi Dideu Medichem Co. Ltd	18192627656	1012@dideu.com	China	3657	58
Dideu Industries Group Limited	+86-29-89586680 +86-15129568250	1026@dideu.com	China	29474	58
Baoji Guokang Bio-Technology Co., Ltd.	0917-3909592 13892490616	gksales1@gk-bio.com	China	9339	58
Baoji Guokang Healthchem co.,ltd	+8615604608665 15604608665	dominicguo@gk-bio.com	CHINA	9427	58
Hefei Hirisun Pharmatech Co., Ltd	+8615056975894	shawn@hirisunpharm.com	CHINA	9923	58
Sinoway Industrial co., ltd.	0592-5800732; +8613806035118	xie@china-sinoway.com	China	992	58

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