We studied the early bactericidal activity of twice standard dose rifampin in subjects with pulmonary tuberculosis evidenced by positive smears. The observed mean 2-day was almost double that reported at dose. Further studies are warranted to establish whether higher doses might assist shortening treatment.

This article describes the population pharmacokinetics of rifampin in South African pulmonary tuberculosis patients. Three datasets containing 2,913 plasma concentration-time data points, collected from 261 patients aged 18 to 72 years and weighing 28.5 85.5 kg receiving regular daily treatment that included administration (450 600 mg) for at least 10 days, were pooled. A compartmental pharmacokinetic model was developed using nonlinear mixed-effects modeling. Variability shape absorption...

Among patients with tuberculosis, rifampin plasma concentrations and sputum conversion rates have been reported to be lower in Africans. Rifampin is a substrate of P-glycoprotein (coded for by the ABCB1 gene) organic anion-transporting polypeptide 1B1 SLCO1B1). The objectives were identify genetic polymorphisms drug transporters transcriptional regulators pregnane X receptor (PXR) constitutive androstane (CAR) an impact on pharmacokinetics South Fifty-seven tuberculosis from Cape Town...

The relationships between antituberculosis drug exposure and treatment effects on humans receiving multidrug therapy are complex nonlinear. In patients treatment, an analysis of the rate decline in sputum bacillary burden reveals two slopes. first is α-slope, which thought to reflect bactericidal effect, followed by a β-slope, sterilizing activity. We sought characterize standard first-line Fifty-four combination for pulmonary tuberculosis clinical trial had concentrations measured...

In most countries with a high burden of tuberculosis, children tuberculosis are prescribed isoniazid at dosages 4-6 mg/kg/day, as recommended by international authorities.We studied concentrations in 56 hospitalized (median age, 3.22 years; interquartile range [IQR], 1.58-5.38 years) who received daily dosage, 5.01 mg/kg/day; range, 2.94-15.58 mg/kg/day) part antituberculosis treatment. At 1 and 4 months after initiation treatment, were measured plasma samples 0.75, 1.5, 3, 4, 6 h treatment...

Objective: Rifampicin dramatically reduces plasma lopinavir concentrations (coformulated with ritonavir in a 4:1 ratio). A study healthy adult volunteers showed that this reduction could be ameliorated if additional is given. We evaluated the effect of on HIV-infected children receiving rifampicin-based treatment for tuberculosis. Methods: measured 2 parallel groups combination antiretroviral therapy included lopinavir-ritonavir, and without antitubercular treatment. Additional was given...

In resource-limited settings, many patients, with no prior protease inhibitor (PI) treatment on a second-line, high genetic barrier, ritonavir-boosted PI-containing regimen have virologic failure.We conducted cross-sectional survey to investigate the aetiology of failure in 2 public health antiretroviral clinics South Africa documenting prevalence (HIV RNA load >500 copies/mL) and genotypic resistance; lopinavir hair plasma concentrations nested case-control study.Ninety-three patients...

This study was designed to characterize the population pharmacokinetics of isoniazid in South African pulmonary tuberculosis patients.Concentration-time measurements obtained from 235 patients receiving oral doses as part routine chemotherapy two clinical studies were pooled and subjected nonlinear mixed-effects analysis.A two-compartmental model, including first-order absorption elimination with allometric scaling, found describe observed dose-exposure relationship for adequately. A mixture...

ABSTRACT Reduced antituberculosis drug concentrations may contribute to unfavorable treatment outcomes among HIV-infected patients with more advanced immune suppression, and few studies have evaluated pharmacokinetics of the first-line drugs in such given fixed-dose combination tablets according international guidelines using weight bands. In this study, were 60 on 4 occasions during first month therapy. Multilevel linear mixed-effects regression analysis was used examine effects age, sex,...

The currently recommended doses of rifampin are believed to be at the lower end dose-response curve. Rifampin induces its own metabolism, although effect dose on extent autoinduction is not known. This study aimed investigate using a semimechanistic pharmacokinetic-enzyme turnover model. Four different structural basic models were explored assess whether scaling methods affected final covariate selection procedure. Covariates selected by linearized approach. model included allometric oral...

Genetic factors, notably CYP2B6 516G→T [rs3745274] and 983T→C [rs28399499], explain much of the interindividual variability in efavirenz pharmacokinetics, but data from Africa are limited. We characterized relationships between genetic polymorphisms plasma concentrations HIV-infected Black South African adults children.Steady-state mid-dosing interval were measured. genotyped 241 genes potentially relevant to metabolism transport, including ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2...

ABSTRACT Rifampin is a key sterilizing drug in the treatment of tuberculosis (TB). It induces its own metabolism, but neither onset nor extent autoinduction has been adequately described. Currently, World Health Organization recommends rifampin dose 8 to 12 mg/kg body weight, which believed be suboptimal, and higher doses may potentially improve outcomes. However, nonlinear increase exposure observed because saturation hepatic extraction hence this should taken into consideration when...

The WHO recommends artemisinin-based combination therapies for treatment of uncomplicated falciparum malaria. At least 15 African countries have adopted artesunate plus amodiaquine as policy. As no pharmacokinetic data on this been published to date, we investigated its interactions and tolerability in healthy volunteers Africa.In a randomized, three-phase, cross-over study, (10 mg/kg) (4 were given single oral doses volunteers. Artesunate was all day 0. On 7 they received either or the...

Rifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli tuberculosis lesions, prevents relapse and thus enables 6-month short-course chemotherapy. Little known about pharmacokinetics rifampin children. The objective this study was to evaluate children with tuberculosis, both human immunodeficiency virus type-1-infected virus-uninfected. Fifty-four children, 21 virus-infected 33 virus-uninfected, mean ages 3.73 4.05 years (P = 0.68),...

Efavirenz is primarily metabolized by CYP2B6, with a minor contribution from CYP1A2, CYP2A6, CYP3A4 and CYP3A5. Genetic variability in these genes contributes towards differences plasma efavirenz concentration, which ultimately leads to either development of adverse drug events or emergence virus resistance. However, the clinical utility validity introducing genotype-assisted dosing not known. The aim this study was therefore evaluate effects 14 single-nucleotide polymorphisms (SNPs) five...

Three new ruthenium complexes with bidentate chloroquine analogue ligands, [Ru(η6-cym)(L1)Cl]Cl (1, cym = p-cymene, L1 N-(2-((pyridin-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine), [Ru(η6-cym)(L2)Cl]Cl (2, L2 N-(2-((1-methyl-1H-imidazol-2-yl)methylamino)ethyl)-7-chloroquinolin-4-amine) and [Ru(η6-cym)(L3)Cl] (3, L3 N-(2-((2-hydroxyphenyl)methylimino)ethyl)-7-chloroquinolin-4-amine) have been synthesized characterized. In addition, the X-ray crystal structure of 2 is reported. The...

ABSTRACT Artemether-lumefantrine and nevirapine-based antiretroviral therapy (ART) are the most commonly recommended first-line treatments for malaria HIV, respectively, in Africa. Artemether, lumefantrine, nevirapine metabolized by cytochrome P450 3A4 enzyme system, which induces, creating potential important drug interactions. In a parallel-design pharmacokinetic study, concentration-time profiles were obtained two groups of HIV-infected patients: ART-naïve patients those stable on...

A long-range coupling across the alkoxycarbonyl group of about 1.4–1.5 G has been observed in EPR spectra radicals formed hydroxyl-radical-initiated homopolymerization methyl acrylate, ethyl and methacrylate within an aqueous flow system at 25°±1°C. This further investigated by way a comprehensive study series simpler, related prepared under similar conditions from formate, acetate, propionate, isobutyrate hydrogen-atom abstraction with hydroxyl radicals. For ester other than those produced...

Ferrocenyl- and aryl-functionalised organosilane thiosemicarbazones.

Background Rifampicin induces expression of the cytochrome P450 isoenzyme 2B6 (CYP2B6), which metabolizes efavirenz. The CYP2B6 516G>T polymorphism impairs efavirenz metabolism and occurs more commonly in Africans than Caucasians. We explored effect rifampicin-based antitubercular therapy on concentrations HIV- infected patients South Africa. Methods Between-patient within-patient comparisons were made mid-dosing interval plasma adults antiretroviral including 600 mg daily, with without...

Objective: Efavirenz-containing regimens using concentration-controlled dosing have been shown to provide potent antiretroviral activity in children. In many settings, is not available. this study, efavirenz plasma concentrations were evaluated South African HIV-infected children receiving efavirenz-based treatment. Methods: Three consecutive blood samples drawn between 12 and 24 hours after 15 the recommended daily doses of efavirenz. Validated liquid chromatography tandem mass spectrometry...