Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in advanced development. This study was undertaken to investigate its effects on thrombin generation. In this placebo-controlled, randomized, crossover study, 12 healthy subjects received rivaroxaban (single 5- or 30-mg dose) placebo. Thrombin generation investigated by measuring the endogenous potential and prothrombinase-induced clotting time. Maximal effect of observed 2 hours after drug administration: time prolonged 1.8...

A finite number of variants in the OPRM1, COMT, MC1R, ABCB1 and CYP2D6 genes has been identified to significantly modulate effects opioids controlled homogenous settings. We analyzed imprint these opioid therapy a highly variable cohort pain patients treated outpatient units test whether genotyping may play role this clinical setting.In multicenter study conducted tertiary care centers, 352 (156 men 196 women, aged 58.5+/- 14.6 years) for 1-600 months (63.4 +/- 92.4 months) with various...

Addictive behavior is importantly mediated by mesolimbic dopaminergic signaling. Here, we comprehensively analyzed the DRD2 gene locus, and in addition, ANKK1 rs1800497C>T single nucleotide polymorphism (SNP), formerly known as 'dopamine D2 receptor Taq1A C>T polymorphism', for associations with risk of opiate addiction methadone dosage requirements.Allelic frequencies DRD2/ANKK1 polymorphisms were compared between 85 methadone-substituted Caucasian patients a random sample 99 healthy...

Background. To determine the rate of seroconversion after 2 doses a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in human immunodeficiency virus type 1 (HIV-1)–infected patients (ClinicalTrials.gov NCT01017172). Methods. Diagnostic study adult HIV-1–infected scheduled for A vaccination. Blood samples where taken before and 21 days first dose second vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay....

To determine rates of seroconversion after single vaccination with a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in HIV-1-infected patients (ClinicalTrials.gov Identifier: NCT01017172).Single center diagnostic study.Institutional HIV outpatient department an urban university clinic.Adult individuals.Serum samples were taken before and 21 days vaccination.Antibody titers determined by hemagglutination inhibition assay. Seroconversion to...

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease presenting with acute edema of subcutaneous tissues and/or mucous membranes. Patients HAE have abnormally low or dysfunctional C1-inhibitor (C1-INH). Preventing the progression attacks main goal C1-INH replacement therapy; knowledge concentrate half-life crucial importance. This pharmacokinetic study was conducted to investigate pharmacokinetics pasteurized human plasma-derived (pC1-INH).This prospective,...

Summary Treatment with the direct thrombin inhibitor argatroban (ARG) is often followed by vitamin K-antagonist treatment (VKA). Phenprocoumon (PC) and acenocoumarol (AC) are frequently used in Europe. The standard monitoring test for VKA, prothrombin time (PT), prolonged inhibitors. Therefore International Normalized Ratio (INR) obtained during combined does not reflect true effect of VKA. A similar interference VKA on activated partial thromboplastin (aPTT), a assay inhibitors, can occur....

ObjectivesThe number of HIV-infected patients receiving orthotopic liver transplantation (OLTX) is increasing. One major challenge the severe drug–drug interactions between immunosuppressive drugs such as tacrolimus and ritonavir-boosted HIV-1 protease inhibitors (PIs). The introduction raltegravir, which not metabolized by cytochrome system, may allow concomitant treatment without dose adaptation.

To assess the pharmacokinetic interaction of saquinavir and lopinavir/ritonavir.Patients from Frankfurt HIV cohort with limited reverse transcriptase inhibitor (RTI) options received protease (PI) combination (soft-gel capsules, 1000 mg twice a day) plus lopinavir/ritonavir (400/100 day), without RTI (LOPSAQ group). A control group same doses ritonavir two to three (RITSAQ steady-state 12 h assessment was performed.Plasma levels saquinavir, lopinavir were determined by liquid...

Summary. Immune tolerance induction (ITI) in haemophilia B patients with inhibitor should be carefully considered because of the relatively poor (25%) overall success rate and high risk complications. ITI combination an immunosuppressive treatment was started two children factor IX (FIX) inhibitor. To avoid anaphylactic reactions boost, FIX replacement therapy stopped received a recombinant activated VII (rFVIIa). After disappearance inhibitor, mycophenolate‐mofetil (MMF), dexamethasone...

To evaluate the pharmacokinetics of nevirapine and any possible influencing factors in pregnant women (n = 16), nonpregnant 13) men 14), who received 200 mg twice daily together with nucleoside reverse transcriptase inhibitors.Blood samples were taken for 12 h at steady state. Nevirapine concentrations measured by liquid chromatography-tandem mass spectrometry. The influence gender, age, body weight comedication on minimum maximum (C(min), C(max)), area under concentration-time curve (AUC),...

Objectives Reduced-function variants of the guanosine triphosphate cyclohydrolase gene (GCH1) have been associated with reduced pain in well-defined cohorts patients and healthy volunteers. We addressed question whether this genetic association plays a role outpatient therapy. Methods In cross-sectional observational study, 523 were enrolled 3 different tertiary care centers at German University hospitals. Of 519 Caucasian patients, data from 424 could be analyzed for functional associations...

Pharmacokinetic differences, contributing to drug-related side effects, between men and women have been reported for HIV protease inhibitors. As only limited inconclusive data on ritonavir-boosted atazanavir are available, we evaluated the respective steady-state pharmacokinetics in 48 male 26 female HIV-1-infected adults receiving atazanavir/ritonavir 300/100 mg once-daily as part of their antiretroviral therapy.Pharmacokinetic profiles (24 h) were assessed measured by HPLC/tandem mass...

ABSTRACT Nonlinear mixed-effects modeling was applied to explore the relationship between lopinavir and ritonavir concentrations over 72 h following drug cessation also assess other dosing strategies compared standard 400-mg–100-mg twice-daily dose. Data from 16 healthy volunteers were included. Possible covariates influencing pharmacokinetics assessed. modeled first separately then together by using individually predicted pharmacokinetic parameters in final model. The model evaluated means...

The objective of this study was to identify parameters among saquinavir pharmacokinetics, patients' demographics or comedications, be addressed for improved personalized therapy. presence human immunodeficiency virus type 1 (HIV-1) RNA at therapy week 48 (principal target parameter), CD4 cell count 48, infections and side effects during weeks, indicators liver toxicity lipid abnormalities a 12-h plasma concentration-versus-time profile were assessed in 56 patients receiving...

Background A saquinavir/ritonavir-containing regimen is one option for the prevention of mother-to-child transmission HIV during pregnancy. We evaluated pharmaco-kinetics, efficacy and safety saquinavir/ritonavir 1,000/100 mg twice daily plus nucleos(t)ide reverse transcriptase inhibitors in 13 women late pregnancy compared results to those 15 non-pregnant women. Methods Protease inhibitor plasma concentration profiles were assessed at 12 h using a standardized therapeutic drug monitoring...

The objective of this study was to evaluate the pharmacokinetics atazanavir (ATV), saquinavir (SQV), and ritonavir (RTV) in a boosted double-protease inhibitor (PI) therapy regimen without reverse transcriptase inhibitors (RTIs). design as follows. Patients with limited RTI options received PI combination 300/100 mg ATV/RTV once daily 1,000 SQV twice (group 1; n=49) comedication. results were compared plasma concentrations PIs patients taking either 300 ATV/100 RTV plus RTIs 2; n=72) or...

In the past, bleeding events have been described for patients with haemophilia taking HIV-1 protease inhibitors. Recently, FDA published a warning concerning intracranial haemorrhage in inhibitor tipranavir co-administered ritonavir. We investigated (i) platelet aggregation vivo HIV-1-infected adult (n = 5) immediately before and 2 4 h after dosing of tipranavir/ritonavir 500/200 mg. To further characterize effects, we then evaluated (ii) (iii) thromboxane B2 (TxB2) formation (ELISA)...

Thromboembolic complications under antiretroviral therapy (ART) have been described in the past. In particular, influence of protease inhibitors (PIs) on platelet activation and coagulation is currently discussion. HIV-1-infected, PI-naive adults (n = 18) were investigated before 4 weeks after start ART, consisting either boosted PI regimens 13) plus reverse transcriptase (RTIs) or a double regimen 5) without RTI co-medication. Administered PIs saquinavir 15), lopinavir 4), fosamprenavir 2)...

To evaluate predictive factors for therapy outcome of a boosted double-protease inhibitor (PI) regimen in 58 extensively pre-treated patients with HIV.Patients received lopinavir/ritonavir 400/100 mg and saquinavir 1,000 twice daily without reverse transcriptase inhibitors (RTI). The primary parameter was HIV RNA < 400 copies/ml at week 48, secondary parameters were HIV-1 CD4+ T-cell count changes from baseline to 48. Pharmacokinetics, genotypic resistance clinical individual correlated the...