Clinical Perspective on Drug?Drug Interactions with the Non-nucleoside Reverse Transcriptase Inhibitor Rilpivirine.

AIDS Rev. 2013 May 17; 15(2): 87-101
Crauwels H, van Heeswijk RP, Stevens M, Buelens A, Vanveggel S, Boven K, Hoetelmans R

Rilpivirine (TMC278) is a non-nucleoside reverse transcriptase inhibitor approved in combination with other antiretrovirals for the treatment of HIV?1 infection in treatment?naive adults (Edurant® 25 mg once daily; Complera® [USA]/Eviplera® [EU] once daily single?tablet regimen). Rilpivirine should be administered with a meal to optimize bioavailability. Its solubility is pH dependent. Rilpivirine is primarily excreted via the feces with negligible renal elimination. Rilpivirine is predominantly metabolized by cytochrome P450 3A4. There is no clinically relevant effect of age, gender, bodyweight, race, estimated glomerular filtration rate, or hepatitis B/C coinfection status on rilpivirine pharmacokinetics in adults. Drug?drug interactions were investigated with cytochrome P450 3A substrates, inducers and inhibitors, drugs altering intragastric pH, antiretrovirals, and other often coadministered drugs. Rilpivirine 25 mg once daily does not have a clinically relevant effect on exposure of coadministered drugs. Coadministration with cytochrome P450 3A inhibitors (ketoconazole, ritonavir?boosted protease inhibitors, telaprevir) results in increased rilpivirine plasma concentrations, but these are not considered clinically relevant; no dose adjustments are required. Coadministration of rilpivirine with cytochrome P450 3A inducers (e.g. rifampin, rifabutin) or compounds increasing gastric pH (e.g. omeprazole, famotidine) results in decreased rilpivirine plasma concentrations, which may increase the risk of virologic failure and resistance development. Therefore, strong cytochrome P450 3A inducers and proton?pump inhibitors are contraindicated. Histamine?2 receptor antagonists and antacids can be coadministered with rilpivirine, provided doses are temporally separated. No dose adjustments are required when rilpivirine is coadministered with: acetaminophen, phosphodiesterase type 5 inhibitors (sildenafil, etc.), atorvastatin (and other statins), oral contraceptives (ethinyl estradiol, norethindrone), chlorzoxazone (cytochrome P450 2E1 substrate), methadone, digoxin, tenofovir disoproxil fumarate, didanosine and other nuceos(t)ide reverse transcriptase inhibitors, and HIV integrase inhibitors (raltegravir, dolutegravir, GSK1265744).
HubMed – Methadone

Electrocatalytic oxidation and selective determination of an opioid analgesic methadone in the presence of acetaminophen at a glassy carbon electrode modified with functionalized multi-walled carbon nanotubes: Application for human urine, saliva and pharmaceutical samples analysis.

Colloids Surf B Biointerfaces. 2013 Apr 17; 109C: 287-293
Amiri-Aref M, Raoof JB, Ojani R

For the first time, electrocatalytic oxidation and selective determination of methadone (Mtd), as a long-acting opioid, in the presence of acetaminophen (Ac) has been investigated at a glassy carbon electrode modified with functionalized multi-walled carbon nanotubes. This simple and sensitive electrochemical sensor was fabricated through the drop-casting of functionalized multi-walled carbon nanotubes (fMWCNT) on the surface of a glassy carbon electrode (GCE). The electrocatalytic oxidations of Ac and Mtd are both individually and simultaneously investigated at the surface of the fMWCNT modified glassy carbon electrode (fMWCNT/MGCE) through using cyclic and differential pulse voltammetric studies. The fMWCNT/MGCE offered a considerable enhancement in the anodic peak current of Ac and Mtd associated with separating their overlapping voltammetric responses with potential difference of 290mV. The catalytic peak currents obtained from differential pulse voltammetry of Ac and Mtd increased linearly with their concentration at the ranges of 0.45-90.0?M and 0.5-100.0?M, respectively, and the detection limits for Ac and Mtd were sequentially 0.35?M and 0.28?M. Furthermore, this electrochemical sensor was successfully implemented for the quantitative determination of Ac and Mtd in human urine, saliva and pharmaceutical samples using standard addition method and the obtained results were found to be satisfactory.
HubMed – Methadone

Highly sensitive capillary electrophoresis-mass spectrometry for rapid screening and accurate quantitation of drugs of abuse in urine.

Anal Chim Acta. 2013 May 30; 780: 101-9
Kohler I, Schappler J, Rudaz S

The combination of capillary electrophoresis (CE) and mass spectrometry (MS) is particularly well adapted to bioanalysis due to its high separation efficiency, selectivity, and sensitivity; its short analytical time; and its low solvent and sample consumption. For clinical and forensic toxicology, a two-step analysis is usually performed: first, a screening step for compound identification, and second, confirmation and/or accurate quantitation in cases of presumed positive results. In this study, a fast and sensitive CE-MS workflow was developed for the screening and quantitation of drugs of abuse in urine samples. A CE with a time-of-flight MS (CE-TOF/MS) screening method was developed using a simple urine dilution and on-line sample preconcentration with pH-mediated stacking. The sample stacking allowed for a high loading capacity (20.5% of the capillary length), leading to limits of detection as low as 2ngmL(-1) for drugs of abuse. Compound quantitation of positive samples was performed by CE-MS/MS with a triple quadrupole MS equipped with an adapted triple-tube sprayer and an electrospray ionization (ESI) source. The CE-ESI-MS/MS method was validated for two model compounds, cocaine (COC) and methadone (MTD), according to the Guidance of the Food and Drug Administration. The quantitative performance was evaluated for selectivity, response function, the lower limit of quantitation, trueness, precision, and accuracy. COC and MTD detection in urine samples was determined to be accurate over the range of 10-1000ngmL(-1) and 21-1000ngmL(-1), respectively.
HubMed – Methadone

The Vinyards Testimony 4 – Instantly heal from a120 milligrams of methadone Testimony.

More Methadone Treatment Information…

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