The relationship between cholesterol crystals, foamy macrophages and haemosiderin in odontogenic cysts

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Outcomes of modern antiretroviral therapy in obese individuals living with HIV

Obesity is a global epidemic and people living with HIV (PLWH) are showing similar obesity trends to those in the general population. Obesity is manifested by several physiological features that can alter volume of distribution, elimination and metabolism of various medications including ART. Some drugs are increasingly prone to pharmacokinetic alteration during obesity depending on their physicochemical properties and clearance mechanism. These considerations raise concerns of hampered efficacy, development of resistance or increased toxicity of ART in PLWH. Here, we summarize available literature on the exposure and antiviral outcomes of currently available antiretroviral drugs in the context of obesity and provide a panel of recommendations for the clinical management and follow-up in this growing patient population

Raltegravir-based Postnatal HIV Prophylaxis Therapy in a Neonate After in Utero Dolutegravir Exposure

We present a case report of a neonate receiving raltegravir-based postnatal HIV prophylaxis after in utero dolutegravir exposure. High levels of raltegravir and dolutegravir can potentially cause bilirubin toxicity as they compete for albumin binding and follow the same metabolic pathway through UGT1A1. This case suggests delaying initiation of raltegravir-based postnatal prophylaxis by 24–48 hours after in utero dolutegravir exposure

Effect of fosamprenavir/ritonavir on the pharmacokinetics of single-dose olanzapine in healthy volunteers

Psychosis and other mental illnesses are common in HIV-infected patients. Olanzapine is one of the preferred antipsychotic agents for the treatment of schizophrenia. Olanzapine is primarily metabolised by CYP1A2 and uridine diphosphate glucuronosyltransferase (UGT). High-dose ritonavir has been shown to increase olanzapine elimination through induction of CYP1A2 and/or UGT, but the effect of low-dose ritonavir on olanzapine pharmacokinetics is unknown. Fosamprenavir is an HIV protease inhibitor that is boosted by low-dose ritonavir. To compensate for the induction of olanzapine metabolism by fosamprenavir/ritonavir, we hypothesised that a dose increase of olanzapine to 15mg with fosamprenavir/ritonavir would lead to a similar area under the concentration-time curve (AUC) compared with olanzapine 10mg alone. An open-label, randomised, two-period, cross-over, single-centre trial was conducted in 24 healthy volunteers. Subjects were randomised to one of the following treatments: (A) fosamprenavir/ritonavir 700/100mg twice daily (b.i.d.) for 16 days with a single dose of olanzapine 15mg on Day 13, a wash-out period of 31 days and a single dose of olanzapine 10mg on Day 48; or (B) the same medication in reverse order. Twenty subjects completed the trial. The geometric mean ratios (90% CI) of olanzapine AUClast, maximum drug concentration (Cmax) and apparent elimination half-life (t1/2) when taken with fosamprenavir/ritonavir versus olanzapine alone were 1.00 (0.93-1.08), 1.32 (1.18-1.47) and 0.68 (0.63-0.74), respectively. Fosamprenavir/ritonavir 700/100mg b.i.d. appeared to induce olanzapine metabolism. We therefore propose a 50% dosage increase of olanzapine when combining with a ritonavir-boosted protease inhibitor

Effect of Pregnancy and Concomitant Antiretrovirals on the Pharmacokinetics of Tenofovir in Women With HIV Receiving Tenofovir Disoproxil Fumarate-Based Antiretroviral Therapy Versus Women With HBV Receiving Tenofovir Disoproxil Fumarate Monotherapy

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Assessment of Maternal and Fetal Dolutegravir Exposure by Integrating Ex Vivo Placental Perfusion Data and Physiologically-Based Pharmacokinetic Modeling

Contains fulltext : 220606.pdf (publisher's version ) (Open Access)Antiretroviral therapy during pregnancy reduces the risk of vertical HIV-1 transmission. However, drug dosing is challenging as pharmacokinetics (PK) may be altered during pregnancy. We combined a pregnancy physiologically-based pharmacokinetic (PBPK) modeling approach with data on placental drug transfer to simulate maternal and fetal exposure to dolutegravir (DTG). First, a PBPK model for DTG exposure in healthy volunteers was established based on physiological and DTG PK data. Next, the model was extended with a fetoplacental unit using transplacental kinetics obtained by performing ex vivo dual-side human cotyledon perfusion experiments. Simulations of fetal exposure after maternal dosing in the third trimester were in accordance with clinically observed DTG cord blood data. Furthermore, the predicted fetal trough plasma concentration (Ctrough ) following 50 mg q.d. dosing remained above the concentration that results in 90% of viral inhibition. Our integrated approach enables simulation of maternal and fetal DTG exposure, illustrating this to be a promising way to assess DTG PK during pregnancy

Prediction of Fetal Darunavir Exposure by Integrating Human Ex-Vivo Placental Transfer and Physiologically Based Pharmacokinetic Modeling

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Pharmacokinetic drug-drug interaction study between raltegravir and citalopram

BACKGROUND: Depression is the most common mental health disorder among HIV-infected patients. When treating HIV-infected patients with a selective serotonin reuptake inhibitor (SSRI), potential drug-drug interactions with antiretroviral agents have to be taken into account. We investigated the two-way pharmacokinetic drug-drug interaction and tolerability of concomitant administration of the SSRI citalopram and the HIV-1 integrase inhibitor raltegravir in healthy volunteers. METHODS: An open-label, crossover, two-period trial was conducted in 24 healthy volunteers. Subjects received the following treatments: citalopram 20 mg once daily for 2 weeks followed by the combination with raltegravir 400 mg twice daily for 5 days and after a washout period raltegravir 400 mg twice daily for 5 days. Intensive steady-state pharmacokinetic blood sampling was performed. Geometric mean ratios (GMRs) of the combination versus the reference treatment and 90% CIs were calculated for the area under the plasma concentration-time curve (AUC). CYP2C19 genotyping was performed because it influences N-demethylation of citalopram to desmethylcitalopram. RESULTS: A total of 22 healthy volunteers completed the trial. GMRs (90% CI) were 1.00 (0.98, 1.03) for citalopram AUC0-24 h, 0.99 (0.88, 1.12) for desmethylcitalopram AUC0-24 h and 0.77 (0.50, 1.19) for raltegravir AUC0-12 h. Raltegravir plasma concentration 12 h after intake (C12 h) did not change with concomitant use of citalopram. Within each CYP2C19 phenotype subgroup the citalopram metabolite-to-parent ratio, which is a measure for metabolic enzyme activity, was not influenced by concomitant raltegravir use. CONCLUSIONS: Raltegravir does not influence the pharmacokinetics of citalopram and desmethylcitalopram. Citalopram did not change the pharmacokinetics of raltegravir in a clinically meaningful way. The combination was well tolerated and can be administered without dose adjustments. ClinicalTrials.gov NCT01978782

Crushing of dolutegravir fixed-dose combination tablets increases dolutegravir exposure

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First pharmacokinetic data of bictegravir in pregnant women living with HIV

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