scholarly journals Effect of Dihydroartemisinin-Piperaquine on the Pharmacokinetics of Praziquantel for Treatment of Schistosoma mansoni Infection

2021 ◽  
Vol 14 (5) ◽  
pp. 400
Author(s):  
Omary Mashiku Minzi ◽  
Rajabu Hussein Mnkugwe ◽  
Eliford Ngaimisi ◽  
Safari Kinung’hi ◽  
Anna Hansson ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Schistosoma Mansoni ◽  
Geometric Mean ◽  
Plasma Samples ◽  
Geometric Mean Ratio ◽  
Post Dose ◽  
Follow Up Study ◽  
Intestinal Schistosomiasis

Praziquantel (PZQ) and dihydroartemisinin-piperaquine (DHP) combination recently showed superior effectiveness than PZQ alone to treat intestinal schistosomiasis. In this follow-up study, we investigated the effect of DHP co-administration on the pharmacokinetics of PZQ and its enantiomers among 64 Schistosoma mansoni infected children treated with PZQ alone (n = 32) or PZQ + DHP combination (n = 32). Plasma samples collected at 0, 1, 2, 4, 6, and 8 h post-dose were quantified using UPLCMS/MS. The geometric mean (GM) of AUCs for total PZQ, R-PZQ and S-PZQ were significantly higher among children who received PZQ + DHP than PZQ alone. The geometric mean ratio (GMR) and (90% CI) of AUC0–∞ for PZQ + DHP to PZQ for total PZQ, R-PZQ, and S-PZQ were 2.18 (1.27, 3.76), 3.98 (2.27, 7.0) and 1.86 (1.06, 3.28), respectively. The GMR and (90% CI) of AUC0–8 for total PZQ, R-PZQ, and S-PZQ were 1.73 (1.12, 2.69), 2.94 (1.75, 4.92), and 1.50 (0.97, 2.31), respectively. The GM of Cmax for total PZQ, R-PZQ and S-PZQ were significantly higher among those who received PZQ + DHP than PZQ alone. The GMR (90% CI) of Cmax of PZQ + DHP to PZQ for total PZQ, R-PZQ, and S-PZQ were 1.75 (1.15, 2.65), 3.08 (1.91, 4.96), and 1.50 (1.0, 2.25%), respectively. The 90% CI of the GMRs for both AUCs and Cmax for total PZQ, R-PZQ, and S-PZQ were outside the acceptable 0.80–1.25 range, indicating that the two treatment arms were not bioequivalent. DHP co-administration significantly increases systemic PZQ exposure, and this may contribute to increased effectiveness of PZQ + DHP combination therapy than PZQ alone to treat schistosomiasis.

A 15-year follow-up study on schistosomiasis in a low-endemic area in Rio de Janeiro State, Brazil

2009 ◽  
Vol 84 (3) ◽  
pp. 229-233 ◽  
Author(s):  
R.P. Igreja ◽  
M.F. Gusmão ◽  
M.G.M. Barreto ◽  
M.T. Paulino ◽  
J.F. da Silva ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Rio De Janeiro ◽  
Endemic Area ◽  
Leisure Activities ◽  
Young Males ◽  
Follow Up Study ◽  
Low Prevalence ◽  
Janeiro State ◽  
Epidemiological Situation

AbstractFifteen years after our first investigation, a follow-up study was carried out with the purpose of assessing the evolution of schistosomiasis in the locality of Sabugo, Paracambi, state of Rio de Janeiro, Brazil, an area with low prevalence of the disease. The coprological techniques adopted were spontaneous sedimentation and Kato-Katz. Out of the 1356 individuals assessed, 13 (1%) were infected with Schistosoma mansoni. From those, 10 were males, 12 were over 15 years old, and at least 11 had been infected in Sabugo. All patients presented either the intestinal or the hepato-intestinal form of the disease, and 8 (61.5%) harboured light parasitic loads. In 1990, there were 27 (2.7%) infected individuals; less than half harboured light parasitic loads, with the predominance of moderate and heavy forms. Although our results indicate an improvement in the epidemiological situation of schistosomiasis in Sabugo, transmission of the disease in the locality is still active, especially among young males, and tends to be acquired during leisure activities.

Pharmacokinetics of fixed-dose combination of tenofovir disoproxil fumarate, lamivudine, and efavirenz: results of a randomized, crossover, bioequivalence study

2016 ◽  
Vol 28 (5) ◽  
pp. 491-498 ◽  
Author(s):  
Dhiraj Abhyankar ◽  
Ashish Shedage ◽  
Milind Gole ◽  
Preeti Raut
Keyword(s):  
Tenofovir Disoproxil Fumarate ◽  
Geometric Mean ◽  
Bioequivalence Study ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Geometric Mean Ratio ◽  
Open Label ◽  
Post Dose ◽  
Dose Combination ◽  
The Individual

The objective of this study was to assess the bioequivalence between a fixed-dose combination of tenofovir disoproxil fumarate/lamivudine/efavirenz 300/300/600 mg and the individual innovator products. A randomized, balanced, open-label, two-sequence, two-treatment, two-period, single dose, crossover study in 48 healthy adults was conducted. Dosing was separated by a washout period of 32 days. Twenty-seven blood samples were collected in each period from pre-dose to 72 h post-dose. The data of 45 subjects were analyzed for pharmacokinetics and safety. Ninety percent CIs of geometric mean ratio on Cmax, AUC0–t, and AUC0-inf for tenofovir and lamivudine and on Cmax and AUC0-72 for efavirenz were within the acceptance criteria (80–125%). For tenofovir disoproxil fumarate, the Tmax, Kel, and t1/2 values for the test and reference products were 1.02 versus 0.91 h, 0.04 versus 0.04/h, 18.67 versus 18.46 h, respectively. For lamivudine, the Tmax, Kel, and t1/2 values were: 1.38 versus 1.30 h, 0.21 versus 0.19/h, 3.44 versus 3.91 h, respectively. For efavirenz, the Tmax values for the test and reference products were 3.71 and 3.65 h, respectively. Both the treatments were well tolerated. Our findings suggest that the tested formulation is bioequivalent to the innovators’ formulations, and both treatments were well tolerated.

scholarly journals Pharmacokinetic Parameters and Tissue Withdrawal Intervals for Sheep Administered Multiple Oral Doses of Meloxicam

Animals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2797
Author(s):  
Sarah Depenbrock ◽  
Tara Urbano ◽  
Jessie Ziegler ◽  
Scott Wetzlich ◽  
Maaike O. Clapham ◽  
...  
Keyword(s):  
Regulatory Agency ◽  
Multiple Dose ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Plasma Samples ◽  
Follow Up Study ◽  
Sample Data ◽  
Oral Doses ◽  
Plasma Pharmacokinetic

Meloxicam is an anti-inflammatory drug used to treat pain and inflammation in ruminants including sheep, and pharmacokinetic studies are needed to protect the food supply from drug residues after use in food-producing animals. This study estimated plasma pharmacokinetic parameters and meat withdrawal intervals (WDI) for market sheep after multiple daily oral doses of meloxicam. Single and multiple dose plasma pharmacokinetic studies, a multi-dose tissue depletion study, and a follow-up study to investigate if events prior to slaughter were associated with differences in plasma meloxicam concentrations, all using sample data collected after completion of dosing, were completed. Using regulatory agency methods for calculating withdrawal times, an estimated WDI of at least 10 d following the last dose is recommended for market lambs treated with 10 daily oral 1 mg/kg doses of meloxicam tablets suspended in water. The effect of events surrounding slaughter on plasma meloxicam concentrations in lambs is unknown but should be considered if plasma samples are obtained immediately prior to or during the slaughter process and used for pharmacokinetic investigations.

A Phase 1, Open Label Study To Evaluate The Drug Interaction Potential With Ketoconazole and The Effect Of Food On The Plasma Pharmacokinetics Of The Smoothened Inhibitor PF-04449913

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3857-3857
Author(s):  
M.Naveed Shaik ◽  
Robert R LaBadie ◽  
Dan Rudin ◽  
Wendy J. Levin
Keyword(s):  
Geometric Mean ◽  
Random Effect ◽  
Geometric Mean Ratio ◽  
Open Label ◽  
Post Dose ◽  
Fed State ◽  
Fasted State ◽  
Effect Of Food ◽  
Plasma Pharmacokinetics ◽  
Anti Fungal

Abstract Introduction PF-04449913 is a potent and selective inhibitor of the Hedgehog signaling pathway through binding to the target, Smoothened (SMO). PF-04449913 inhibits Hedgehog (Hh) signaling ex vivo and has demonstrated anti-tumor activity in vivo. PF-04449913 is currently under clinical evaluation in the AML and high risk MDS patient populations, who receive anti-fungal agents routinely as prophylaxis. The preferred anti-fungal agents are azoles which are known strong CYP3A4 inhibitors. Preliminary assessment using individual recombinant P450 enzymes suggests that CYP3A4 plays a major role in mediating the metabolism of PF-04449913. Preliminary results show that PF-04449913 does not inhibit CYPs .Thus, one of the goals of this study was to understand the potential drug-drug interaction (DDI) impact of a strong CYP3A4 inhibitor (ketoconazole) on PF-04449913 plasma exposure to provide dosing guidance. An additional objective was to estimate the effect of a high fat, high calorie meal on single dose PF-04449913 plasma pharmacokinetics (PK). Methods This was an open label, 2-sequence, 3-period, 3-treatment arm, single dose, crossover study in healthy volunteers. Subjects were randomized to receive single doses of 200 mg PF-04449913 in either the fasted or fed state during Periods 1 or 2 with a washout period of at least 8 days between treatments. Subsequently, in Period 3, all subjects received a fixed regimen of ketoconazole (400 mg/day) from Days 1 to 7 and a co-administered single 200 mg PF-04449913 dose on Day 4. Serial blood sampling to determine plasma concentrations of PF-04449913 was performed to 120 hours post dose in Periods 1 and 2, and to 144 hours post dose in Period 3. PF-04449913 in the fasted state was the Reference treatment for both comparisons, while PF-04449913 in the fed state and PF-04449913 + ketoconazole were the Test treatments. Natural log transformed AUCinf (area under the plasma concentration versus time curve from time zero to infinity) and Cmax (maximum observed plasma concentration) for PF-04449913 were analyzed using a mixed effects model with sequence, period and treatment as fixed effects and subject within sequence as a random effect for the effect of food. For the DDI, natural log transformed AUCinf and Cmax for PF-04449913 were analyzed using a mixed effects model with treatment as a fixed effect and subject as a random effect. The adjusted mean differences and 90% confidence intervals (CIs) for the differences from both models were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. Results PF-04449913 exposure was increased in the presence of ketoconazole, with a geometric mean ratio for AUCinf of 2.40 (90% CI: 2.15 -2.68) and for Cmax of 1.40 (90% CI: 1.24-1.58). For PF-04449913 alone and with ketoconazole, Cmax occurred 1.0 and 2.0 hours after dosing, respectively. The geometric mean ratio for AUCinf for fed state compared to the fasted state was 0.87 (90% CI: 0.78 -0.97) and for Cmax was 0.66 (90% CI: 0.56-0.78). In the fasted and fed state, the PF-0444913 Cmax occurred at 1.0 and 4.0 hours after dosing, respectively. All adverse events (AE) were mild in severity except for one case of moderate AE accelerated idioventricular rhythm in an individual with underlying cardiac issues, which was classified as non-treatment related. Conclusions PF-04449913 plasma exposures and peak concentrations were increased (2.40-fold for AUCinf and 1.40-fold for Cmax) following concurrent administration of ketoconazole in healthy volunteers. These findings provide the upper limit for the PF-04449913 plasma exposures expected with potent metabolic inhibition and define PF-04449913 dosing parameters in AML and high-risk MDS patient trials. While PF-04449913 plasma exposures and peak concentrations were decreased following administration of PF-04449913 in the fed state, the difference in exposures under the fed and fasted conditions was not considered clinically meaningful. Disclosures: Shaik: Pfizer: Employment, Stock Other. LaBadie:Pfizer: Employment, Stock Other. Rudin:Pfizer: Employment. Levin:Pfizer Oncology Business Unit: Employment.

Electron Microscopy of Human Gallstones

1971 ◽  
Vol 29 ◽  
pp. 296-297
Author(s):  
C. Wolpers ◽  
R. Blaschke
Keyword(s):  
Electron Microscopy ◽  
Room Temperature ◽  
Bile Pigment ◽  
X Ray Diffraction ◽  
Triclinic Crystal System ◽  
X Ray ◽  
Follow Up Study ◽  
Infra Red ◽  
Main Components

Scanning microscopy was used to study the surface of human gallstones and the surface of fractures. The specimens were obtained by operation, washed with water, dried at room temperature and shadowcasted with carbon and aluminum. Most of the specimens belong to patients from a series of X-ray follow-up study, examined during the last twenty years. So it was possible to evaluate approximately the age of these gallstones and to get information on the intensity of growing and solving.Cholesterol, a group of bile pigment substances and different salts of calcium, are the main components of human gallstones. By X-ray diffraction technique, infra-red spectroscopy and by chemical analysis it was demonstrated that all three components can be found in any gallstone. In the presence of water cholesterol crystallizes in pane-like plates of the triclinic crystal system.

A 10-year follow-up study of fixed metal ceramic prosthodontics

1997 ◽  
Vol 24 (10) ◽  
pp. 713-717 ◽  
Author(s):  
R. NAPANKANGAS ◽  
M.A.M. SALONEN ◽  
A.M. RAUSTIA
Keyword(s):  
Follow Up Study ◽  
Metal Ceramic
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