Population Pharmacokinetic Model of N-acetylmannosamine (ManNAc) and N-acetylneuraminic acid (Neu5Ac) in Subjects with GNE Myopathy.

Background: GNE myopathy is a rare genetic muscle disease resulting from deficiency in an enzyme critical for the biosynthesis of N-acetylneuraminic acid (Neu5Ac, sialic acid). The uncharged Neu5Ac precursor, N-acetylmannosamine (ManNAc), is under development as an orphan drug for treating GNE myopathy.

Methods: A semi-mechanistic population pharmacokinetic model was developed to simultaneously characterize plasma ManNAc and its metabolite Neu5Ac following oral administration of ManNAc to subjects with GNE myopathy.

Race/Ethnicity and Protease Inhibitor Use Influence Plasma Tenofovir Exposure in Adults Living with HIV-1 in AIDS Clinical Trials Group Study A5202.

AIDS Clinical Trial Group study A5202 (ClinicalTrials.gov identifier NCT00118898) was a phase 3b, randomized, partially blinded equivalence study of open-label atazanavir/ritonavir or efavirenz, plus either placebo-controlled tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, in treatment-naive adults living with HIV-1, evaluating efficacy, safety, and tolerability. We report an analysis of the contribution of participant characteristics to the disposition of tenofovir plasma concentrations.

Efavirenz Therapeutic Range in HIV-1 Treatment-Naive Participants.

Background: Efavirenz is currently suggested as an alternative to recommended antiretroviral (ARV) regimens by the Department of Health and Human Services for the treatment of HIV-1 in ARV-naive patients. A mid-dosing interval therapeutic range between 1000 and 4000 ng/mL for efavirenz has been proposed in the literature, with patients more likely to experience virologic failure below this range and adverse effects above. The current study reports an analysis of virologic outcome between those above, below, or within the reported efavirenz therapeutic range (1000-4000 ng/mL) and within subgroups.

Pharmacokinetic Considerations for Combining Antiretroviral Therapy, Direct-Acting Antiviral Agents for Hepatitis C Virus, and Addiction Treatment Medications.

There are many factors that can affect the pharmacokinetics (PK) of drugs. Pathophysiological changes from disease states can alter the mechanisms that control the PK of antiretrovirals (ARVs), direct-acting antivirals (DAAs), and addiction treatment medications. Drug-drug interaction pathways of certain ARVs and DAAs can be very complex, with agents being substrates, inhibitors, or inducers of multiple metabolic and transporter pathways.

Development and validation of a UPLC-MS/MS method for the simultaneous determination of paritaprevir and ritonavir in rat liver.

Aim: Determination of paritaprevir and ritonavir in rat liver tissue samples.

Results: We successfully validated a UPLC-MS/MS method to measure paritaprevir and ritonavir in rat liver using deuterated internal standards (d8-paritapervir and d6-ritonavir). The method is linear from 20 to 20,000 and 5 to 10,000 pg on column for paritaprevir and ritonavir, respectively, and is normalized per milligram tissue.

Recent advances in management of the HIV/HCV coinfected patient.

Chronic hepatitis C virus (HCV) is a global epidemic, affecting approximately 150 million individuals throughout the world. The implications of HCV infection have been magnified in those who are infected with both HCV and the HIV as liver disease progression, liver failure and liver-related death are increased, particularly in those without well-controlled HIV disease. The development of direct-acting antiviral agents for HCV that allow shorter treatment periods with increased efficacy and decreased adverse events have greatly changed the outlook for HCV-infected individuals.