Maraviroc

513.67

513.67

1592732-453-0

MD6P741W8A

DTXSID8048949

C73144

White solid from toluene/hexane (2:1)|White- to pale-colored powder

J05AX09|J - Antiinfectives for systemic use

2934999090

63

5.1

Brown Solid

1.3±0.1 g/cm3

197-198 °C @ Solvent: Toluene, Hexane

1.628

DMSO: >30mg/mL

Store at +4°C

1.09X10-11 mm Hg at 25 deg C (est)

Henry's Law constant = 9.49X10-15 atm-cu m/mol at 25 °C (est)

pKa = 7.3

Highly soluble across the physiological pH range (pH 1.0 to 7.5)|Hydroxyl radical reaction rate constant = 8.27X10-11 cu cm/molec-sec at 25 °C (est)

NONH for all modes of transport

1

48/22

22-36

Xn

Shelf life is 24 months.

P260, P273, P314, P501

H373

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including maraviroc, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H373 (100%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]|P260, P273, P314, and P501|Aggregated GHS information provided by 31 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Therapy with maraviroc was associated with alanine aminotransferase (ALT) elevations in up to 10% of patients, but elevations above 5 times normal are less common. Furthermore, rates of ALT elevations with maraviroc were similar to rates in comparator groups receiving similar background optimized antiretroviral therapy [2.6% vs 3.4% above 5 times ULN in one study and 3.9% vs 4.0% in a second]. These elevations have not been associated with clinical symptoms and generally did not require dose modification. Nevertheless, two cases of acute hepatocellular injury arose in patients receiving maraviroc in prelicensure clinical trials. Both were women, ages 24 and 27, who developed fever, fatigue and rash followed by liver tests abnormalities within 1 to 3 weeks of starting maraviroc. One patient remained anicteric (peak bilirubin 1.5 mg/dL) while the other developed marked jaundice (peak bilirubin 31 mg/dL) and underwent emergency liver transplantation 16 days after onset. In both instances, other potential causes were present but no other diagnosis was confirmed. For these reasons, hepatitis and hepatic failure are listed as adverse events in the product label which includes a boxed warning about hepatotoxicity. Aplaviroc, the initial CCR5 antagonist developed, was abandoned during preclinical testing because of concerns about hepatotoxicity. The clinical features of hepatotoxicity related to maraviroc have not been described in detail and the drug has had limited use. There have been no further reports of liver failure attributed to maraviroc therapy.

Maraviroc is a substrate of the P-glycoprotein transport system, and the possibility exists that drugs that are inhibitors or inducers of this system may alter the pharmacokinetics of maraviroc. Maraviroc inhibits the P-glycoprotein transport system; potential pharmacokinetic interaction (may affect bioavailability of certain other drugs).|Possible pharmacokinetic interaction with carbamazepine, phenobarbital, or phenytoin (decreased plasma concentrations of maraviroc). Recommended dosage of maraviroc is 600 mg twice daily in patients receiving these anticonvulsants, provided the regimen does not include a potent CYP3A inhibitor. Some experts suggest that alternative anticonvulsants be considered in patients receiving maraviroc.|Possible pharmacokinetic interaction with itraconazole (increased plasma concentrations of maraviroc). Recommended dosage of maraviroc is 150 mg twice daily in patients receiving itraconazole.|Pharmacokinetic interaction with ketoconazole (substantially increased plasma concentrations of maraviroc). Recommended dosage of maraviroc is 150 mg twice daily in patients receiving ketoconazole.|For more Interactions (Complete) data for Maraviroc (32 total), please visit the HSDB record page.

Peak plasma concentrations and area under the plasma concentration-time curve (AUC) are higher in individuals with mild or moderate hepatic impairment compared with individuals with normal hepatic function. ... Individuals with moderate hepatic impairment receiving maraviroc 150 mg twice daily and a drug that strongly inhibits CYP3A should be monitored for maraviroc-associated adverse effects. Caution is advised if maraviroc is used in patients with hepatic impairment or with HBV or HCV infection.

Approximately 76% bound to human plasma proteins, with moderate affinity for albumin and alpha-1 acid glycoprotein.

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV infection. Studies in lactating rats indicate that maraviroc is extensively secreted into rat milk. It is not known whether maraviroc is secreted into human milk. Because of the potential for both HIV transmission and serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving maraviroc.

For treatment-experienced adult patients infected with only CCR5-tropic HIV-1 detectable, who have evidence of viral replication and HIV-1 strains resistant to multiple antiretroviral agents.|FDA Label|Celsentri, in combination with other antiretroviral medicinal products, is indicated for treatment experienced adults, adolescents and children of 2 years of age and older and weighing at least 10 kg infected with only CCR5-tropic HIV-1 detectable,|Treatment of human immunodeficiency virus (HIV-1) infection

Maraviroc is a chemokine co-receptor 5 (CCR5) antagonist, the first of a new class of agents active against the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome (AIDS). Maraviroc was approved for use in the United States in 2007 but has had limited use. Maraviroc has been associated with elevations in serum aminotransferase levels and to several cases of acute, clinically apparent liver injury.

Antiviral Agents

Receptors, CCR5/antagonists & inhibitors; HIV Fusion Inhibitors|Maraviroc, in combination with other antiretroviral agents, is indicated for adult patients infected with only CCR5-tropic HIV-1. This indication is based on analyses of plasma HIV-1 RNA levels in two controlled studies of maraviroc in treatment-experienced subjects and one study in treatment-naive subjects. Both studies in treatment-experienced subjects were conducted in clinically advanced, 3-class antiretroviral-experienced (NRTI, NNRTI, PI, or enfuvirtide) adults with evidence of HIV-1 replication despite ongoing antiretroviral therapy. /Included in US product label/

/BOXED WARNING/ Hepatotoxicity has been reported with maraviroc use. Evidence of a systemic allergic reaction (e.g., pruritic rash, eosinophilia or elevated IgE) prior to the development of hepatotoxicity may occur. Patients with signs or symptoms of hepatitis or allergic reaction following use of maraviroc should be evaluated immediately.|Adult patients infected with only CCR5-tropic HIV-1 should use Maraviroc.|Tropism testing must be conducted with a highly sensitive tropism assay that has demonstrated the ability to identify patients appropriate for Maraviroc use. Outgrowth of pre-existing low-level CXCR4- or dual/mixed-tropic HIV-1 not detected by tropism testing at screening has been associated with virologic failure on Maraviroc.|Use of Maraviroc is not recommended in subjects with dual/mixed or CXCR4-tropic HIV-1 as efficacy was not demonstrated in a phase 2 study of this patient group.|For more Drug Warnings (Complete) data for Maraviroc (26 total), please visit the HSDB record page.

HIV-1 variants with reduced susceptibility to maraviroc have been selected in cell culture, following serial passage of two CCR5-tropic viruses (CC1/85 and RU570). The maraviroc-resistant viruses remained CCR5-tropic with no evidence of a change from a CCR5-tropic virus to a CXCR4-using virus. Two amino acid residue substitutions in the V3-loop region of the HIV-1 envelope glycoprotein (gp160), A316T and I323V (HXB2 numbering), were shown to be necessary for the maraviroc-resistant phenotype in the HIV-1 isolate CC1/85. In the RU570 isolate a 3-amino acid residue deletion in the V3 loop, deltaQAI (HXB2 positions 315-317), was associated with maraviroc resistance. The relevance of the specific gp120 mutations observed in maraviroc-resistant isolates selected in cell culture to clinical maraviroc resistance is not known. Maraviroc-resistant viruses were characterized phenotypically by concentration response curves that did not reach 100% inhibition in phenotypic drug assays, rather than increases in EC50 values.|Maraviroc had antiviral activity against HIV-1 clinical isolates resistant to NNRTIs, NRTIs, PIs and the fusion inhibitor enfuvirtide in cell culture (EC50 values ranged from 0.7 to 8.9 nM (0.36 to 4.57 ng/mL)). Maraviroc-resistant viruses that emerged in cell culture remained susceptible to the enfuvirtide and the protease inhibitor saquinavir.|Virologic failure on maraviroc can result from genotypic and phenotypic resistance to maraviroc, through outgrowth of undetected CXCR4-using virus present before maraviroc treatment, through resistance to background therapy drugs, or due to low exposure to maraviroc. Antiretroviral treatment-experienced subjects ... Week 48 data from treatment-experienced subjects failing maraviroc-containing regimens with CCR5-tropic virus (n=58) have identified 22 viruses that had decreased susceptibility to maraviroc characterized in phenotypic drug assays by concentration response curves that did not reach 100% inhibition. Additionally, CCR5-tropic virus from 2 of these treatment failure subjects had greater than or equal to 3-fold shifts in EC50 values for maraviroc at the time of failure. Fifteen of these viruses were sequenced in the gp120 encoding region and multiple amino acid substitutions with unique patterns in the heterogeneous V3 loop region were detected. Changes at either amino acid position 308 or 323 (HXB2 numbering) were seen in the V3 loop in 7 of the subjects with decreased maraviroc susceptibility. Substitutions outside the V3 loop of gp120 may also contribute to reduced susceptibility to maraviroc.

Maraviroc is a chemokine receptor antagonist drug developed by the drug company Pfizer that is designed to act against HIV by interfering with the interaction between HIV and CCR5.

Compounds and drugs that inhibit or block the activity of CCR5 RECEPTORS. (See all compounds classified as CCR5 Receptor Antagonists.)|Inhibitors of the fusion of HIV to host cells, preventing viral entry. This includes compounds that block attachment of HIV ENVELOPE PROTEIN GP120 to CD4 RECEPTORS. (See all compounds classified as HIV Fusion Inhibitors.)

The absolute oral bioavailability of a 100 mg dose is 23% and is predicted to be 33% at 300 mg. Coadministration of a 300mg tablet with a high fat breakfast reduced maraviroc Cmax and AUC by 33% in healthy volunteers.|194 L|... Maraviroc (Celsentri) is an orally administered drug ... Maraviroc plasma exposure is not dose proportional. After a rapid (but moderate) intestinal absorption, several inactive oxidized metabolites are produced via cytochrome P450 3A4 pathway. ...|Peak maraviroc plasma concentrations are attained 0.5-4 hr following single oral doses of 1-1200 mg administered to uninfected volunteers.|The absolute bioavailability of a 100 mg dose is 23% and is predicted to be 33% at 300 mg. Maraviroc is a substrate for the efflux transporter P-glycoprotein.|Coadministration of a 300mg tablet with a high fat breakfast reduced maraviroc Cmax and AUC by 33% in healthy volunteers. There were no food restrictions in the studies that demonstrated the efficacy and safety of maraviroc. Therefore, maraviroc can be taken with or without food at the recommended dose.|For more Absorption, Distribution and Excretion (Complete) data for Maraviroc (12 total), please visit the HSDB record page.

In vitro studies indicate that CYP3A is the major enzyme responsible for maraviroc metabolism.|Maraviroc is the major circulating component ( approximately 42% drug-related radioactivity) following a single oral dose of 300 mg(14)C-maraviroc. The most significant circulating metabolite in humans is a secondary amine (approximately 22% radioactivity) formed by N-dealkylation. This polar metabolite has no significant pharmacological activity. Other metabolites are products of mono-oxidation and are only minor components of plasma drug-related radioactivity.|Studies in humans and in vitro studies using human liver microsomes and expressed enzymes have demonstrated that maraviroc is principally metabolized by the cytochrome P450 system to metabolites that are essentially inactive against HIV-1. In vitro studies indicate that CYP3A is the major enzyme responsible for maraviroc metabolism. In vitro studies also indicate that polymorphic enzymes CYP2C9, CYP2D6 and CYP2C19 do not contribute significantly to the metabolism of maraviroc.|... Maraviroc is extensively metabolized by CYP3A4, with renal clearance accounting for approximately 23% of total clearance. ...

14-18 hours|The terminal half-life of maraviroc following oral dosing to steady state in healthy subjects was 14-18 hours.|... The half-life of maraviroc is approximately 16 hr. ...

Maraviroc is an entry inhibitor and works by blocking HIV from entering human cells. Specifically maraviroc is a selective, slowly reversible, small molecule antagonist of the interaction between human CCR5 and HIV-1 gp120. Maraviroc selectively binds to the human chemokine receptor CCR5 present on the membrane of CD4 cells (T-cells), preventing the interaction of HIV-1 gp120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells.|Maraviroc, a synthetic antiretroviral agent, is an HIV entry inhibitor. The drug is a small molecule CCR5 antagonist. HIV enters host cells by attaching to the CD4+ T-cell receptor using 1 of 2 chemokine co-receptors, CCR5 or CXCR4. Maraviroc selectively binds to CCR5 on the cell membrane and prevents the interaction of HIV-1 glycoprotein 120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells. Maraviroc does not inhibit entry of CXCR4-tropic and dual/mixed-tropic HIV-1 into cells. CCR5 is a co-receptor for the most commonly transmitted HIV-1 strains that predominate during the early stages of infection; this form remains the dominant form in many patients with late-stage infection. Maraviroc is active against some strains of HIV-1 resistant to nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs), HIV protease inhibitors (PIs), and HIV entry and fusion inhibitors (enfuvirtide). HIV-1 strains with reduced susceptibility to maraviroc have been produced in vitro and have emerged during maraviroc therapy.|Maraviroc is a member of a therapeutic class called CCR5 co-receptor antagonists. Maraviroc selectively binds to the human chemokine receptor CCR5 present on the cell membrane, preventing the interaction of HIV-1 gp120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells. CXCR4-tropic and dual-tropic HIV-1 entry is not inhibited by maraviroc.|Maraviroc inhibits the replication of CCR5-tropic laboratory strains and primary isolates of HIV-1 in models of acute peripheral blood leukocyte infection. The mean EC50 value (50% effective concentration) for maraviroc against HIV-1 group M isolates (subtypes A to J and circulating recombinant form AE) and group O isolates ranged from 0.1 to 4.5 nM (0.05 to 2.3 ng/mL) in cell culture. ... Maraviroc was not active against CXCR4-tropic and dual-tropic viruses (EC50 value >10 uM). The antiviral activity of maraviroc against HIV-2 has not been evaluated.|Maraviroc (MVC, Celsentri) is an allosteric and reversible inhibitor of the CCR5 chemokine coreceptor. ... MVC exclusively inhibits the replication of R5- tropic HIV-1 variants after binding to the transmembrane CCR5 receptor cavity.|For more Mechanism of Action (Complete) data for Maraviroc (6 total), please visit the HSDB record page.

There is no specific antidote for overdose with maraviroc. Treatment of overdose should consist of general supportive measures including keeping the patient in a supine position, careful assessment of patient vital signs, blood pressure and ECG.|Administration of activated charcoal may also be used to aid in removal of unabsorbed drug. Since maraviroc is moderately protein-bound, dialysis may be beneficial in removal of this medicine.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ A placebo-controlled, randomized, crossover study to evaluate the effect on the QT interval of healthy male and female volunteers was conducted with three single oral doses of maraviroc and moxifloxacin. The placebo-adjusted mean maximum (upper 1-sided 95% CI) increases in QTc from baseline after 100, 300 and 900 mg of maraviroc were -2 (0), -1 (1), and 1 (3) msec, respectively, and 13 (15) msec for moxifloxacin 400 mg. No subject in any group had an increase in QTc of >/=60 msec from baseline. No subject experienced an interval exceeding the potentially clinically relevant threshold of 500 msec. Warning: Hepatotoxicity; Hepatotoxicity has been reported which may be preceded by evidence of a systemic allergic reaction (e.g., pruritic rash, eosinophilia or elevated IgE). Immediately evaluate patients with signs or symptoms of hepatitis or allergic reaction.|/SIGNS AND SYMPTOMS/ The highest dose administered in clinical studies was 1200 mg. The dose-limiting adverse event was postural hypotension, which was observed at 600 mg. While the recommended dose for maraviroc in patients receiving a CYP3A inducer without a CYP3A inhibitor is 600 mg twice daily, this dose is appropriate due to enhanced metabolism. Prolongation of the QT interval was seen in dogs and monkeys at plasma concentrations 6 and 12 times, respectively, those expected in humans at the intended exposure of 300 mg equivalents twice daily. However, no significant QT prolongation was seen in the studies in treatment-experienced subjects with HIV using the recommended doses of maraviroc or in a specific pharmacokinetic study to evaluate the potential of maraviroc to prolong the QT interval.|/SIGNS AND SYMPTOMS/ Hepatotoxicity has been reported with maraviroc use. Evidence of a systemic allergic reaction (e.g., pruritic rash, eosinophilia or elevated IgE) prior to the development of hepatotoxicity may occur. Patients with signs or symptoms of hepatitis or allergic reaction following use of maraviroc should be evaluated immediately.|/OTHER TOXICITY INFORMATION/ ... Maraviroc is associated with bronchitis, nasopharyngitis, and esophageal candidiasis. ...|/OTHER TOXICITY INFORMATION/ No characteristic adverse effect of maraviroc has been identified. ... Nor was there any evidence of an increase in the incidence of neoplasms or serious infections in patients treated with maraviroc. In a study on naive patients, maraviroc produced nonsignificant changes in total cholesterol, LDL, HDL and triglycerides. Although CCR5 co-receptors play a role in the immune response of the body, it has not been shown whether individuals homozygote for its deletion (delta-32 mutation) have an increased risk of serious infections, with the possible exception of encephalitis due to the West Nile virus. However, long-term follow up is required on patients treated with to be able to rule out any increased susceptibility to infections or neoplasms.

4,4-difluoro-N-((1S)-3-(exo-3-(3-isopropyl-5-methyl-4H-1,2,4-triazol-4-yl)-8-azabicyclo(3.2.1)oct-8-yl)-1-phenylpropyl)cyclohexanecarboxamide

Table: Maraviroc Preparations [Table#7978]|Celsentri, 150 mg film-coated tablet.

Made in Ireland

The method for determination of maraviroc (UK-427,857) and its major metabolite (UK-408,027) in human plasma consists of a protein-precipitation procedure and analysis by liquid chromatography/tandem mass spectrometry using positive ion TurboIonSpray ionization and multiple reaction monitoring. The assay has been validated over a concentration range of 0.500-500 ng/mL for both analytes. The determinations of maraviroc in human cerebrospinal fluid (0.500-500 ng/mL) and in urine (5.00-5000 ng/mL) have also been validated but do not include measurement of the metabolite.|... A new HPLC-UV method to quantify simultaneously maraviroc and raltegravir levels in human plasma is reported. ... The volume of the plasma sample was 600 microL. This method involved automated solid-phase extraction with Oasis HLB Cartridge 1 cc (30 mg divinylbenzene and N-vinylpyrrolidone) and evaporation in a water bath under nitrogen stream. The extracted samples were reconstituted with 200 microL 50/50 of mobile-phase solution (0.01 M KH(2)PO(4) and acetonitrile). Twenty microliters of these samples were injected into a HPLC-UV system, the analytes were eluted on an analytical dC18 Atlantis column (150 mm x 4.6 mm I.D.) with a particle size of 5 microm. The mobile phase (0.01 M KH(2)PO(4) and acetonitrile) was delivered at 1.0 mL/min with isocratic elution. The total run time for a single analysis was 10 min; maraviroc and raltegravir were detected by UV at 197 and 300 nm. The calibration curves were linear up to 2,500 ng/mL. The absolute recovery ranged between 93 and 100%. The HPLC-UV method reported here has been validated and is currently applied to monitor plasma levels of maraviroc and raltegravir in HIV-infected patients.|Raltegravir (RAL), maraviroc (MVC), darunavir (DRV), and etravirine (ETV) are new antiretroviral agents with significant potential for drug interactions. This work describes a sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of plasma drug levels. Single-step extraction of RAL, MVC, DRV, ETV and RTV from plasma (100 microl) is performed by protein precipitation using 600 microl of acetonitrile, after the addition of 100 microl darunavir-d(9) (DRV-d(9)) at 1000 ng/ml in MeOH/H(2)O 50/50 as internal standard (I.S.). The mixture is vortexed, sonicated for 10 min, vortex-mixed again and centrifuged. An aliquot of supernatant (150 microl) is diluted 1:1 with a mixture of 20 mM ammonium acetate/MeOH 40/60 and 10 microl is injected onto a 2.1 x 50 mm Waters Atlantis-dC18 3 microm analytical column. Chromatographic separations are performed using a gradient program with 2 mM ammonium acetate containing 0.1% formic acid and acetonitrile with 0.1% formic acid. Analyte quantification is performed by electrospray ionisation-triple quadrupole mass spectrometry using the selected reaction monitoring detection in the positive mode. The method has been validated over the clinically relevant concentrations ranging from 12.5 to 5000 ng/ml, 2.5 to 1000 ng/ml, 25 to 10,000 ng/ml, 10 to 4000 ng/ml, and 5 to 2000 ng/ml for RAL, MRV, DRV, ETV and RTV, respectively. The extraction recovery for all antiretroviral drugs is always above 91%. The method is precise, with mean inter-day CV% within 5.1-9.8%, and accurate (range of inter-day deviation from nominal values -3.3 to +5.1%). In addition our method enables the simultaneous assessment of raltegravir-glucuronide. This is the first analytical method allowing the simultaneous assay of antiretroviral agents targeted to four different steps of HIV replication. The proposed method is suitable for the Therapeutic Drug Monitoring Service of these new regimen combinations administered as salvage therapy to patients having experienced treatment failure, and for whom exposure, tolerance and adherence assessments are critical.|/Investigators/ developed a conventional LC-MS method for determining plasma maraviroc concentrations, validated by estimating precision and accuracy for inter- and intraday analysis in the concentration range of 0.011-2.188 ug/mL. The calibration curve was linear within this range. The average accuracy ranged from 92.7% to 99.7%, while the relative standard deviations of both inter- and intraday assays were less than 7.1%. Recovery of maraviroc exceeded 86.7%. /This/ LC-MS method provides a conventional, accurate and precise way to determine the maraviroc concentration in human plasma. This method enables dose adjustment based on monitoring plasma maraviroc concentrations and permits management of drug interactions and toxicity.

Human drugs -> Celsentri -> EMA Drug Category|Antivirals for systemic use -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients