CYP3A4; HIV

Ritonavir has a mean Ki of 19 nM, making it a very potent inhibitor of CYP3A4-mediated testosterone 6β-hydroxylation. It also has an IC50 of 4.2 μM for tolbutamide hydroxylation.[1]
Ritonavir has a mean Ki of 19 nM, making it a very potent inhibitor of CYP3A4-mediated testosterone 6β-hydroxylation. It also has an IC50 of 4.2 μM for tolbutamide hydroxylation. (Source: ) It is discovered that ritonavir is a strong inhibitor of CYP3A-mediated biotransformations (IC50 values for nifedipine oxidation and 17alpha-ethynylestradiol 2-hydroxylation are 0.07 mM, 2 mM, and 0.14 mM, respectively). The reactions mediated by CYP2D6 (IC50 = 2.5 mM) and CYP2C9/10 (IC50 = 8.0 mM) are also found to be inhibited by ritonavir.[2]
In human PBMC cultures that are not infected, ritonavir increases cell viability. In uninfected human PBMC cultures, ritonavir significantly reduces caspase-3 activity, annexin V staining, and the susceptibility of PBMCs to apoptosis, which is correlated with lower levels of caspase-1 expression. In PBMCs and monocytes, ritonavir inhibits the induction of tumor necrosis factor (TNF) production in a time- and dose-dependent manner at nontoxic concentrations.[3]
Ritonavir has a high affinity for p-glycoprotein as evidenced by its ability to inhibit p-glycoprotein-mediated extrusion of saquinavir, with an IC50 of 0.2 μM.[4] Ritonavir has a 13 nM Ki that potently inhibits the microsomal metabolism of ABT-378 in human liver. Inhibiting CYP3A (IC50 = 1.1 and 4.6 μM), Ritonavir in combination with ABT-378 (at 3:1 and 29:1 ratios) is less effective than Ritonavir (IC50 = 0.14 μM).[5]

PAXLOVID™ (Co-packaging of Nirmatrelvir with ritonavir) has been approved for the treatment of Coronavirus Disease 2019 (COVID-19). The goal of the experiment was to create an accurate and straightforward analytical method using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to simultaneously quantify nirmatrelvir and ritonavir in rat plasma, and to investigate the pharmacokinetic profiles of these drugs in rats. After protein precipitation using acetonitrile, nirmatrelvir, ritonavir, and the internal standard (IS) lopinavir were separated using ultra performance liquid chromatography (UPLC). This separation was achieved with a mobile phase composed of acetonitrile and an aqueous solution of 0.1% formic acid, using a reversed-phase column with a binary gradient elution. Using multiple reaction monitoring (MRM) technology, the analytes were detected in the positive electrospray ionization mode. Favorable linearity was observed in the calibration range of 2.0-10000 ng/mL for nirmatrelvir and 1.0-5000 ng/mL for ritonavir, respectively, within plasma samples. The lower limits of quantification (LLOQ) attained were 2.0 ng/mL for nirmatrelvir and 1.0 ng/mL for ritonavir, respectively. Both drugs demonstrated inter-day and intra-day precision below 15%, with accuracies ranging from -7.6% to 13.2%. Analytes were extracted with recoveries higher than 90.7% and without significant matrix effects. Likewise, the stability was found to meet the requirements of the analytical method under different conditions. This UPLC-MS/MS method, characterized by enabling accurate and precise quantification of nirmatrelvir and ritonavir in plasma, was effectively utilized for in vivo pharmacokinetic studies in rats[8].

Ritonavir (ABT 538) is an inhibitor of testosterone 6β-hydroxylation mediated by CYP3A4, with a mean Ki of 19 nM. It also has an IC50 of 4.2 μM for tolbutamide hydroxylation. It is discovered that ritonavir (ABT 538) is a strong inhibitor of CYP3A-mediated biotransformations (IC50 values for nifedipine oxidation and 17alpha-ethynylestradiol 2-hydroxylation are 0.07 mM, 2 mM, and 0.14 mM, respectively). Inhibitors of the reactions mediated by CYP2D6 (IC50=2.5 mM) and CYP2C9/10 (IC50=8.0 mM) include ritonavir.

In human peripheral blood mononuclear cells that are not infected, ritonavir increases cell viability. In uninfected human PBMC cultures, ritonavir significantly lowers the susceptibility of PBMCs to apoptosis, which is correlated with lower levels of caspase-1 expression, decreases in annexin V staining, and reduces caspase-3 activity. At nontoxic concentrations, ritonavir inhibits the induction of tumor necrosis factor (TNF) production by monocytes and PBMCs in a time- and dose-dependent manner. With an IC50 of 0.2 μM, ritonavir inhibits p-glycoprotein-mediated saquinavir extrusion, suggesting a high affinity for p-glycoprotein. With a Ki of 13 nM, ritonavir potently inhibits the human liver microsomal metabolism of ABT-378. Although less potently than Ritonavir (IC50=0.14 μM), Ritonavir in combination with ABT-378 (at 3:1 and 29:1 ratios) inhibits CYP3A (IC50=1.1 and 4.6 μM).

BALB/c mice
60 mg/kg
i.p.

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Animal experiments[8]
A cohort of six male Sprague-Dawley rats (in good health, and their individual weights falling within the range of 200–220 g) was used. Prior to commencing the experiment, the rats were housed in a controlled environment with clean cages for a week-long acclimation period. The ambient conditions were maintained at 25 °C and a 12-h light/dark cycle. During this time, the animals enjoyed ad libitum access to food and water. Before the day of dosing, a 12-h fasting period was performed, during which water intake remained unrestricted. Each rat was received an oral administration of a solution containing 30 mg/kg of nirmatrelvir and 10 mg/kg of ritonavir, formulated in 0.5% sodium carboxymethylcellulose. At designated time points, including pre-dose (0 h), 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 h post-dosing, approximately 0.3 mL of blood was drawn from the tail vein into heparinized centrifuge tubes. After centrifugation of these samples at 8000×g and 25 °C for 10 min, the supernatant was carefully transferred into fresh tubes and stored at −80 °C pending further analysis.

Pharmacokinetic parameters of nirmatrelvir and ritonavir in each rat, encompassing area under the concentration-time curve (AUC), time to reach peak plasma concentration (Tmax), maximum plasma concentration (Cmax), elimination half-life (t1/2), apparent clearance (CLz/F), and mean residence time (MRT), were analyzed through non-compartmental statistical models using the Drugs and Statistics (DAS 3.0) software. The data were presented as mean ± standard deviation (SD).

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Drug repurposing is a promising strategy for identifying new applications for approved drugs. Here, we describe a polymer biomaterial composed of the antiretroviral drug ritonavir derivative (5-methyl-4-oxohexanoic acid ritonavir ester; RD), covalently bound to HPMA copolymer carrier via a pH-sensitive hydrazone bond (P-RD). Apart from being more potent inhibitor of P-glycoprotein in comparison to ritonavir, we found RD to have considerable cytostatic activity in six mice (IC50 ~ 2.3-17.4 μM) and six human (IC50 ~ 4.3-8.7 μM) cancer cell lines, and that RD inhibits the migration and invasiveness of cancer cells in vitro. Importantly, RD inhibits STAT3 phosphorylation in CT26 cells in vitro and in vivo, and expression of the NF-κB p65 subunit, Bcl-2 and Mcl-1 in vitro. RD also dampens chymotrypsin-like and trypsin-like proteasome activity and induces ER stress as documented by induction of PERK phosphorylation and expression of ATF4 and CHOP. P-RD nanomedicine showed powerful antitumor activity in CT26 and B16F10 tumor-bearing mice, which, moreover, synergized with IL-2-based immunotherapy. P-RD proved very promising therapeutic activity also in human FaDu xenografts and negligible toxicity predetermining these nanomedicines as side-effect free nanosystem. The therapeutic potential could be highly increased using the fine-tuned combination with other drugs, i.e. doxorubicin, attached to the same polymer system. Finally, we summarize that described polymer nanomedicines fulfilled all the requirements as potential candidates for deep preclinical investigation.[7]

Absorption, Distribution and Excretion
The absolute bioavailability of ritonavir has not been determined. Following oral administration, peak concentrations are reached after approximately 2 hours and 4 hours (Tmax) after dosing under fasting and non-fasting conditions, respectively. It should be noted that ritonavir capsules and tablets are not considered bioequivalent.
Ritonavir is primarily eliminated in the feces. Following oral administration of a single 600mg dose of radiolabeled ritonavir, approximately 11.3 ± 2.8% of the dose was excreted into the urine, of which 3.5 ± 1.8% was unchanged parent drug. The same study found that 86.4 ± 2.9% of the dose was excreted in the feces, of which 33.8 ± 10.8% was unchanged parent drug.
The estimated volume of distribution of ritonavir is 0.41 ± 0.25 L/kg.
The apparent oral clearance at steady-state is 8.8 ± 3.2 L/h. Renal clearance is minimal and estimated to be <0.1 L/h.
Ritonavir and its metabolites are eliminated from the body predominantly in the feces (86% of unchanged drug and metabolites), with minor urinary elimination (11%, mostly metabolites).
Absorption of ritonavir is only slightly affected by diet, and this is somewhat dependent on the formulation. The overall absorption of ritonavir from the capsule formulation may increase by 15% when taken with meals. ... There is greater than sixfold variability in drug trough concentrations among patients given 600 mg of ritonavir every 12 hours.
The extent of oral absorption is high and is not affected by food. Within the clinical concentration range, ritonavir is approximately 98 to 99% bound to plasma proteins, including albumin and alpha 1-acid glycoprotein. Cerebrospinal fluid (CSF) drug concentrations are low in relation to total plasma concentration. However, parallel decreases in the viral burden have been observed in the plasma, CSF and other tissues. ... About 34% and 3.5% of a 600 mg dose is excreted as unchanged drug in the feces and urine, respectively. The clinically relevant t1/2 beta is about 3 to 5 hours. Because of autoinduction, plasma concentrations generally reach steady state 2 weeks after the start of administration. The pharmacokinetics of ritonavir are relatively linear after multiple doses, with apparent oral clearance averaging 7 to 9 L/hr.
Ritonavir is excreted principally in the feces, both as unchanged drug and metabolites. Following oral administration of 600 mg of radiolabeled ritonavir as the oral solution, 86.4% of the dose is excreted in feces (33.8% as unchanged drug) and 11.3% of the dose is excreted in urine (3.5% as unchanged drug).
For more Absorption, Distribution and Excretion (Complete) data for RITONAVIR (6 total), please visit the HSDB record page.

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Metabolism / Metabolites
Ritonavir circulates in the plasma predominantly as unchanged drug. Five metabolites have been identified. The isopropylthiazole oxidation metabolite (M-2) is the major metabolite in low plasma concentrations and retains similar antiviral activity to unchanged ritonavir. The cytochrome P450 enzymes CYP3A and CYP2D6 are the enzymes primarily involved in the metabolism of ritonavir.
... Ritonavir is primarily metabolised by cytochrome P450 (CYP) 3A isozymes and, to a lesser extent, by CYP2D6. Four major oxidative metabolites have been identified in humans, but are unlikely to contribute to the antiviral effect. ...
Five ritonavir metabolites have been identified in human urine and feces. The isopropylthiazole oxidation metabolite (M2) appears to be the major metabolite. M2 (but not other metabolites) has antiviral activity similar to that of ritonavir; however, only very low concentrations of this metabolite are present in plasma. Other metabolites identified in in vitro studies include a decarbamoylated metabolite (M1) and a product of N-dealkylation at the urea terminus (M11).

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Biological Half-Life
The approximate half-life of ritonavir is 3-5 hours.
The clinically relevant t1/2 beta is about 3 to 5 hours.

Hepatotoxicity
Some degree of serum aminotransferase elevations occurs in a high proportion of patients taking ritonavir containing antiretroviral regimens. Moderate-to severe elevations in serum aminotransferase levels (>5 times the upper limit of normal) are found in up to 15% of patients treated with full doses of ritonavir and are more common in patients with HIV-HCV coinfection. With low “booster” doses, ritonavir does not appear to increase the frequency or severity of serum enzyme elevations, and those that occur are usually asymptomatic and self-limited, resolving even with continuation of ritonavir. Clinically apparent liver injury from full doses of ritonavir has been reported, but hepatotoxicity from low dose ritonavir has not been clearly linked to acute liver injury. In many situations, the liver injury is difficult to attribute to ritonavir because it is used in combination with higher doses of other protease inhibitors. HIV protease inhibitors have been associated with acute liver injury arising 1 to 8 weeks after onset, with variable patterns of liver enzyme elevation, from hepatocellular to cholestatic. Immunoallergic features (rash, fever, eosinophilia) are uncommon as is autoantibody formation. Ritonavir in combination with saquinavir has also been associated with a rapid onset (1 to 4 days) acute hepatic injury in patients who are taking rifampin and perhaps other agents that affect CYP 450 activity, such as phenobarbital. Finally, initiation of ritonavir based highly active antiretroviral therapy can lead to exacerbation of an underlying chronic hepatitis B or C in coinfected individuals, typically arising 2 to 12 months after starting therapy and associated with a hepatocellular pattern of serum enzyme elevations and increases followed by falls in serum levels of hepatitis B virus (HBV) DNA or hepatitis C virus (HCV) RNA. Ritonavir therapy has not been clearly linked to lactic acidosis and acute fatty liver that is reported in association with several nucleoside analogue reverse transcriptase inhibitors.
Likelihood score: C (probable rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Ritonavir is excreted into milk in measurable concentrations and low levels can be found in the blood of some breastfed infants. No adverse reactions in breastfed infants have been reported. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Protein Binding
Ritonavir is highly protein-bound in plasma (~98-99%), primarily to albumin and alpha-1 acid glycoprotein over the standard concentration range.

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Interactions
These medications /amiodarone, astemizole, bepridil, bupropion, cisapride, clozapine, dihydroergotamine, encainide, ergotamine, flecainide, meperidine, pimozide, piroxicam, propafenone, propoxyphene, quinidine, rifabutin or terfenadine/ should not be administered concurrently with ritonavir; concurrent administration with ritonavir is likely to produce a large increase in the plasma concentrations of these medications, which may increase the risk of arrhythmias, hematologic abnormalities, seizures, or other potentially serious adverse effects.
In one study, concurrent administration /with clarithromycin/ increased the AUC of clarithromycin by 77% and the peak plasma concentration by 31%; dosing does not need to be adjusted in patients with normal renal function; however, for patients with a creatinine clearance of 30 to 60 ml/minute (0.5 to 1 ml/second), the dose of clarithromycin should be reduced by 50%, and for patients with a creatinine clearance of less than 30 ml/minute (0.5 ml/second), the dose of clarithromycin should be reduced by 75%.
These medications /clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam, or zolpidem/ should not be administered concurrently with ritonavir; concurrent administration with ritonavir is likely to produce a large increase in the plasma concentrations of these medications, which may produce extreme sedation and respiratory depression.
In one study, concurrent administration /with estrogen-containing oral contraceptive/ decreased the AUC of ethinyl estradiol by 40%; an oral contraceptive with a higher estrogen content or an alternative method of contraception should be considered.
For more Interactions (Complete) data for RITONAVIR (14 total), please visit the HSDB record page.

[1]. Br J Clin Pharmacol . 1997 Aug;44(2):190-4.

[2]. J Pharmacol Exp Ther . 1996 Apr;277(1):423-31.

[3]. J Hum Virol . 1999 Sep-Oct;2(5):261-9.

[4]. Biochem Pharmacol . 1999 May 15;57(10):1147-52.

[5]. Drug Metab Dispos . 1999 Aug;27(8):902-8.

[6]. Nat Med . 2018 May;24(5):604-609.

[7]. J Control Release . 2021 Apr 10:332:563-580.

[8]. Heliyon . 2024 May 30;10(11):e32187.

Therapeutic Uses
Ritonavir is indicated in combination with nucleoside analogs or as monotherapy for the treatment of HIV infection or AIDS. /Included in US product labeling/
Lopinavir/ritonavir has demonstrated antiviral activity in the HIV-infected adult. The objective of this study was to investigate a liquid coformulation of lopinavir/ritonavir, in combination with reverse transcriptase inhibitors, in HIV-infected children. One hundred antiretroviral (ARV)-naive and ARV-experienced, nonnucleoside reverse transcriptase inhibitor-naive children between 6 months and 12 years of age participated in this Phase I/II, open label, multicenter trial. Subjects initially received either 230/57.5 mg/sq m or 300/75 mg/sq m lopinavir/ritonavir twice daily; ARV-naive subjects also received stavudine and lamivudine, whereas ARV-experienced subjects also received nevirapine and one or two nucleoside reverse transcriptase inhibitors. Lopinavir/ritonavir pharmacokinetics, safety and efficacy were evaluated. All subjects were escalated to the 300/75 mg/sq m twice daily dose based on results from an interim pharmacokinetic and safety evaluation. The pharmacokinetics of lopinavir did not appear to be dependent on age when dosing was based on body surface area but were decreased on coadministration with nevirapine. Overall 79% of subjects had HIV RNA levels <400 copies/mL at Week 48 (intent-to-treat: missing = failure). Mean increases in absolute and relative (percent) CD4 counts from baseline to Week 48 were observed in both ARV-naive subjects (404 cells/cu mm; 10.3%) and ARV-experienced subjects (284 cells/cu mm; 5.9%). Only one subject prematurely discontinued the study because of a study drug-related adverse event. The liquid coformulation of lopinavir/ritonavir demonstrated durable antiviral activity and was safe and well-tolerated after 48 weeks of treatment in HIV-infected children.

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Drug Warnings
The most frequent adverse effects associated with ritonavir therapy involve the GI tract. In one clinical study in HIV-infected patients, nausea occurred in 25.6%, vomiting in 13.7%, diarrhea in 15.4%, taste perversion in 11.1%, abdominal pain in 6%, local throat irritation in 1.7%, anorexia in 1.7%, and flatulence in 0.9% of patients who received ritonavir monotherapy. In clinical studies in patients with HIV infection who received ritonavir in conjunction with nucleoside antiretroviral therapy or ritonavir in conjunction with saquinavir, nausea occurred in 18.4-46.6%, vomiting in 7.1-23.3%, diarrhea in 22.7-25%, taste perversion in 5-17.2%, anorexia in 4.3-8.6%, abdominal pain in 2.1-8.3%, local throat irritation in 0.9-2.8%, and flatulence in 1.7-3.5% of patients. Constipation, dyspepsia, or fecal incontinence occurred in 0.2-3.4, 0.7-5.9, or 2.8%, respectively, of patients receiving ritonavir with other antiretroviral agents; these effects were not reported in patients receiving ritonavir monotherapy. Many adverse GI effects reported with ritonavir are transient; vomiting persists for an average of 1 week, nausea for 2-3 weeks, and diarrhea for 5 weeks.
Adverse GI effects reported in less than 2% of patients receiving ritonavir alone or in conjunction with other antiretroviral agents include abnormal stools, bloody diarrhea, cheilitis, cholangitis, colitis, dry mouth, dysphagia, enlarged abdomen, eructation, esophageal ulcer, esophagitis, gastritis, gastroenteritis, GI disorder, GI hemorrhage, gingivitis,ileus, melena, mouth ulcer, pseudomembranous colitis, rectal disorder, rectal hemorrhage, sialadenitis, stomatitis, taste loss, tenesmus, thirst, tongue edema, and ulcerative colitis.
Peripheral paresthesia occurred in 6% and paresthesia or circumoral paresthesia occurred in 2.6-3.4% of patients with HIV infection receiving ritonavir monotherapy in one clinical study (study 245). In clinical studies in patients receiving ritonavir in conjunction with nucleoside antiretroviral therapy (studies 245 and 247) or in conjunction with saquinavir (study 462), peripheral paresthesia was reported in 55.7%, paresthesia in 2.1-5.2%, and circumoral paresthesia in 5.2-6.7% of patients. Asthenia occurred in 10.3% of patients receiving ritonavir monotherapy and in 15.3-28.4% of patients receiving ritonavir with other antiretroviral agents. Many of these adverse effects are transient; peripheral paresthesia persists for an average of 34 weeks and circumoral paresthesia and asthenia persist for 35 weeks.
Dizziness, insomnia, or somnolence have been reported in 2.6% of patients receiving ritonavir monotherapy and in 3.9-8.5, 2-3.4, or 2.4-2.6%, respectively, of patients receiving ritonavir with other antiretroviral agents. Headache, depression, or abnormal thinking were reported in 4.3-7.8, 1.7-7.1, or 0.7-2.6%, respectively, of patients receiving ritonavir in conjunction with other antiretroviral agents. Anxiety or confusion were reported in up to 2.1% of patients receiving ritonavir with other antiretroviral agents.
For more Drug Warnings (Complete) data for RITONAVIR (34 total), please visit the HSDB record page.

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Pharmacodynamics
Ritonavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Ritonavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. Modern protease inhibitors require the use of low-dose ritonavir to boost pharmacokinetic exposure through inhibition of metabolism via the cytochrome P450 3A4 enzyme pathway.

C37H48N6O5S2

720.94

720.312

C, 61.64; H, 6.71; N, 11.66; O, 11.10; S, 8.90

155213-67-5

Ritonavir-d6;1616968-73-0;rel-Ritonavir-d6;1217720-20-1;Ritonavir metabolite;176655-55-3;Ritonavir-13C,d3

392622

White to off-white solid powder

1.2±0.1 g/cm3

947.0±65.0 °C at 760 mmHg

120-122°C

526.6±34.3 °C

0.0±0.3 mmHg at 25°C

1.600

5.28

4

9

18

50

1040

4

S1C([H])=C(C([H])([H])N(C([H])([H])[H])C(N([H])[C@]([H])(C(N([H])[C@@]([H])(C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])C([H])([H])[C@@]([H])([C@]([H])(C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])N([H])C(=O)OC([H])([H])C2=C([H])N=C([H])S2)O[H])=O)C([H])(C([H])([H])[H])C([H])([H])[H])=O)N=C1C([H])(C([H])([H])[H])C([H])([H])[H]

NCDNCNXCDXHOMX-XGKFQTDJSA-N

InChI=1S/C37H48N6O5S2/c1-24(2)33(42-36(46)43(5)20-29-22-49-35(40-29)25(3)4)34(45)39-28(16-26-12-8-6-9-13-26)18-32(44)31(17-27-14-10-7-11-15-27)41-37(47)48-21-30-19-38-23-50-30/h6-15,19,22-25,28,31-33,44H,16-18,20-21H2,1-5H3,(H,39,45)(H,41,47)(H,42,46)/t28-,31-,32-,33-/m0/s1

1,3-thiazol-5-ylmethyl N-[(2S,3S,5S)-3-hydroxy-5-[[(2S)-3-methyl-2-[[methyl-[(2-propan-2-yl-1,3-thiazol-4-yl)methyl]carbamoyl]amino]butanoyl]amino]-1,6-diphenylhexan-2-yl]carbamate

ABT-538; A 84538; Norvir; ABT538; Norvir; ABT-538; A-84538; Abbott 84538; ABBOTT-84538; Empetus; A-84538; Norvir Sec; 538, ABT; Ritonavir; ABT 538;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 2.5 mg/mL (3.47 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (3.47 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 2.5 mg/mL (3.47 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 4: 2.5 mg/mL (3.47 mM) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 5: 0.5 mg/mL (0.69 mM) in 1% DMSO 99% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 6: 30% PEG400+0.5% Tween80+5% propylene glycol: 30 mg/mL

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 (Please use freshly prepared in vivo formulations for optimal results.)