scholarly journals Effects of Gender, AIDS, and Acetylator Status on Intrapulmonary Concentrations of Isoniazid

2002 ◽  
Vol 46 (8) ◽  
pp. 2358-2364 ◽  
Author(s):  
John E. Conte ◽  
Jeffrey A. Golden ◽  
Mari McQuitty ◽  
Juliana Kipps ◽  
Sheila Duncan ◽  
...  
Keyword(s):  
High Performance ◽  
Slow Acetylators ◽  
Dilution Method ◽  
Study Group ◽  
Alveolar Cells ◽  
Entire Study ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Acetylator Status ◽  
Adult Volunteers

ABSTRACT The objective of the present study was to evaluate the effects of gender, AIDS, and acetylator status on the steady-state concentrations of orally administered isoniazid in plasma and lungs. Isoniazid was administered at 300 mg once daily for 5 days to 80 adult volunteers. Subjects were assigned to eight blocks according to gender, presence or absence of AIDS, and acetylator status. Blood was obtained prior to administration of the first dose, 1 h after administration of the last dose, and at the completion of bronchoscopy and bronchoalveolar lavage (BAL), which was performed 4 h after administration of the last dose. The metabolism of caffeine was used to determine acetylator status. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method. Isoniazid concentrations in plasma, BAL fluid, and alveolar cells (ACs) were measured by high-performance liquid chromatography. AIDS status or gender had no significant effect on the concentrations of isoniazid in plasma at 1 or 4 h. Concentrations in plasma at 4 h and concentrations in ELF were greater in slow acetylators than fast acetylators. The concentration in plasma (1.85 ± 1.60 μg/ml [mean ± standard deviation; n = 80]) at 1 h following administration of the last dose was not significantly different from that in ELF (2.25 ± 3.50 μg/ml) or ACs (2.61 ± 5.01 μg/ml). For the entire study group, concentrations in plasma at 1 h were less than 1.0, 2.0, and 3.0 μg/ml for 34.7, 60, and 82.7% of the subjects, respectively; concentrations in ELF were less than 1.0, 2.0, and 3.0 μg/ml in 30 (37.5%), 53 (66.0%), and 58 (72.5%) of the subjects, respectively; and concentrations in ACs were less than 1.0, 2.0, and 3.0 μg/ml in 43 (53.8%), 59 (73.8%), and 65 (81.3%) of the subjects, respectively. The concentrations of orally administered isoniazid in plasma were not affected by gender or the presence of AIDS. The concentrations in plasma at 4 h and the concentrations in ELF, but not the concentrations in ACs, were significantly greater in slow acetylators than fast acetylators. Concentrations in plasma and lungs were low compared to recommended therapeutic concentrations in plasma and published MICs of isoniazid for Mycobacterium tuberculosis. The optimal concentrations of isoniazid in ACs and ELF are unknown, but these data suggest that the drug enters these compartments by passive diffusion and achieves concentrations similar to those found in plasma.

scholarly journals Intrapulmonary Concentrations of Pyrazinamide

1999 ◽  
Vol 43 (6) ◽  
pp. 1329-1333 ◽  
Author(s):  
John E. Conte ◽  
Jeffrey A. Golden ◽  
Sheila Duncan ◽  
Elaine McKenna ◽  
Elisabeth Zurlinden
Keyword(s):  
High Performance ◽  
Cell Counting ◽  
Dilution Method ◽  
High Concentration ◽  
Alveolar Cells ◽  
Women Subjects ◽  
The Difference ◽  
Normal Women ◽  
Normal Men ◽  
Adult Volunteers

ABSTRACT The objective of this study was to compare the steady-state plasma and intrapulmonary concentrations of orally administered pyrazinamide in normal volunteers and subjects with AIDS. Pyrazinamide was administered at 1 g once daily for 5 days to 40 adult volunteers (10 men with AIDS, 10 normal men, 10 women with AIDS, and 10 normal women). Subjects with AIDS and with more than four stools per day were excluded. Blood was obtained prior to administration of the first dose, 2 h after the last dose, and at the completion of bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Standardized bronchoscopy was performed without systemic sedation. The volume of epithelial lining fluid (ELF) recovered was calculated by the urea dilution method. The total number of alveolar cells (AC) was counted in a hemocytometer, and differential cell counting was performed after cytocentrifugation. Pyrazinamide was measured by high-performance liquid chromatography. The presence of AIDS or gender had no significant effect on the concentrations of pyrazinamide in plasma. The concentrations of pyrazinamide in ELF and AC were lower in the subjects with AIDS than in the subjects without AIDS, but the difference was not significant. The concentrations in plasma (mean ± standard deviation) were 25.1 ± 7.6 and 21.1 ± 6.8 μg/ml at 2 and 4 h after the last dose, respectively, and were not significantly different from the concentration (17.4 ± 16.9 μg/ml) in AC. The concentration of pyrazinamide in ELF was high (431 ± 220 μg/ml) and was approximately 4 to 40 times the reported MIC for pyrazinamide-susceptible strains of Mycobacterium tuberculosis. The high concentration of pyrazinamide in ELF may contribute in part to the effectiveness of the drug in treating pulmonary tuberculosis.

scholarly journals Comparison of Plasma, Epithelial Lining Fluid, and Alveolar Macrophage Concentrations of Solithromycin (CEM-101) in Healthy Adult Subjects

2012 ◽  
Vol 56 (10) ◽  
pp. 5076-5081 ◽  
Author(s):  
Keith A. Rodvold ◽  
Mark H. Gotfried ◽  
J. Gordon Still ◽  
Kay Clark ◽  
Prabhavathi Fernandes
Keyword(s):  
Steady State ◽  
High Performance ◽  
Healthy Adult ◽  
Plasma Concentrations ◽  
Epithelial Lining ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
The Mean

ABSTRACTThe steady-state concentrations of solithromycin in plasma were compared with concomitant concentrations in epithelial lining fluid (ELF) and alveolar macrophages (AM) obtained from intrapulmonary samples during bronchoscopy and bronchoalveolar lavage (BAL) in 30 healthy adult subjects. Subjects received oral solithromycin at 400 mg once daily for five consecutive days. Bronchoscopy and BAL were carried out once in each subject at either 3, 6, 9, 12, or 24 h after the last administered dose of solithromycin. Drug concentrations in plasma, ELF, and AM were assayed by a high-performance liquid chromatography-tandem mass spectrometry method. Solithromycin was concentrated extensively in ELF (range of mean [± standard deviation] concentrations, 1.02 ± 0.83 to 7.58 ± 6.69 mg/liter) and AM (25.9 ± 20.3 to 101.7 ± 52.6 mg/liter) in comparison with simultaneous plasma concentrations (0.086 ± 0.070 to 0.730 ± 0.692 mg/liter). The values for the area under the concentration-time curve from 0 to 24 h (AUC0–24values) based on mean and median ELF concentrations were 80.3 and 63.2 mg · h/liter, respectively. The ratio of ELF to plasma concentrations based on the mean and median AUC0–24values were 10.3 and 10.0, respectively. The AUC0–24values based on mean and median concentrations in AM were 1,498 and 1,282 mg · h/L, respectively. The ratio of AM to plasma concentrations based on the mean and median AUC0–24values were 193 and 202, respectively. Once-daily oral dosing of solithromycin at 400 mg produced steady-state concentrations that were significantly (P< 0.05) higher in ELF (2.4 to 28.6 times) and AM (44 to 515 times) than simultaneous plasma concentrations throughout the 24-h period after 5 days of solithromycin administration.

scholarly journals Effects of AIDS and Gender on Steady-State Plasma and Intrapulmonary Ethionamide Concentrations

2000 ◽  
Vol 44 (5) ◽  
pp. 1337-1341 ◽  
Author(s):  
John E. Conte ◽  
Jeffrey A. Golden ◽  
Mari McQuitty ◽  
Juliana Kipps ◽  
Emil T. Lin ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Antimycobacterial Activity ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Epithelial Lining ◽  
Alveolar Cells ◽  
Epithelial Lining Fluid ◽  
Healthy Men ◽  
And Gender ◽  
Adult Volunteers

ABSTRACT Ethionamide, 250 mg every 12 h for a total of nine doses, was administered to 40 adult volunteers (10 men with AIDS, 10 healthy men, 10 women with AIDS, and 10 healthy women). Blood was obtained for drug assay prior to administration of the first dose, 2 h after the last dose, and at the completion of standardized bronchoscopy and bronchoalveolar lavage, which were performed 4 h after the last dose. Ethionamide was measured in epithelial lining fluid (ELF) and alveolar cells (AC) using a new mass spectrometric method. The presence of AIDS or gender was without significant effect on the concentrations of ethionamide in plasma, AC, or ELF. Plasma concentrations (mean ± standard deviation [SD]) were 0.97 ± 0.65 and 0.65 ± 0.35 μg/ml at 2 and 4 h after the last dose, respectively, and both values were significantly greater than the concentration of ethionamide in AC (0.38 ± 0.47 μg/ml) (P < 0.05). The concentration of ethionamide was significantly greater in ELF (5.63 ± 3.8 μg/ml) than in AC or plasma at 2 and 4 h and was approximately 10 to 20 times the reported MIC for ethionamide-susceptible strains of Mycobacterium tuberculosis. For all 40 subjects, the ELF/plasma concentration ratios (mean ± SD) at 2 and 4 h were 8.7 ± 11.7 and 9.7 ± 5.6, respectively. We conclude that the absorption of orally administered ethionamide, as measured in this study, was not affected by gender or the presence of AIDS. Ethionamide concentrations were significantly greater in ELF than in plasma or AC, suggesting that substantial antimycobacterial activity resides in this compartment.

scholarly journals Intrapulmonary pharmacokinetics of azithromycin in healthy volunteers given five oral doses.

1996 ◽  
Vol 40 (11) ◽  
pp. 2582-2585 ◽  
Author(s):  
K M Olsen ◽  
G San Pedro ◽  
L P Gann ◽  
P O Gubbins ◽  
D M Halinski ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
High Performance ◽  
Blood Monocytes ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Drug Concentrations ◽  
Proven Efficacy ◽  
Study Support ◽  
Oral Doses ◽  
Oral Azithromycin

The intrapulmonary pharmacokinetics of oral azithromycin were studied in 25 healthy volunteers, each of whom received an initial dose of 500 mg and then 250 mg once daily for four additional doses. Bronchoscopy, bronchoalveolar lavage, and venipuncture were performed 4, 28, 76, 124, 172, 244, 340, and 508 h after the first dose was administered. Azithromycin concentrations in epithelial lining fluid (ELF), alveolar macrophages, peripheral blood monocytes, and serum were measured by high-performance liquid chromatography. Azithromycin was extensively concentrated in cells and ELF. Drug concentrations in AMs (peak mean +/- standard deviation, 464 +/- 65 micrograms/ml) exceeded 80 micrograms/ml up to 508 h (21 days) following the first dose, while concentrations in PBMs (peak, 124 +/- 28 micrograms/ml) exceeded 20 micrograms/ml up to 340 h (14 days). Azithromycin concentrations in ELF peaked at 124 h (3.12 +/- 0.93 micrograms/ml) and were detectable up to 172 h (7 days), when they were 20 times the concurrent serum concentrations. Although the clinical significance of antibiotic concentrations in these compartments is nuclear, the sustained lung tissue penetration and extensive phagocytic accumulation demonstrated in this study support the proven efficacy of azithromycin administered on a 5-day dosage schedule in the treatment of extracellular or intracellular pulmonary infections.

Comparison of bronchopulmonary pharmacokinetics of clarithromycin and azithromycin.

1996 ◽  
Vol 40 (10) ◽  
pp. 2375-2379 ◽  
Author(s):  
K B Patel ◽  
D Xuan ◽  
P R Tessier ◽  
J H Russomanno ◽  
R Quintiliani ◽  
...  
Keyword(s):  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Tissue Concentration ◽  
Epithelial Lining ◽  
Assay Sensitivity ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Time Points ◽  
Plasma Pharmacokinetics ◽  
Absolute Concentrations

The bronchopulmonary and plasma pharmacokinetics of clarithromycin (CLA; 500 mg given twice daily for nine doses) or azithromycin (AZ; 500 mg for the first dose and then 250 mg once daily for four doses) were assessed in 41 healthy nonsmokers. Bronchoalveolar lavage was performed at 4, 8, 12, or 24 h after administration of the last dose. The concentrations (mean +/- standard deviation) of CLA, 14-hydroxyclarithromycin, and AZ were measured in plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) cells by high-performance liquid chromatography assay. The concentrations of CLA achieved in ELF were 34.02 +/- 5.16 micrograms/ml at 4 h, 20.63 +/- 4.49 micrograms/ml at 8 h, 23.01 +/- 11.9 micrograms/ml at 12 h, and 4.17 +/- 0.29 microgram/ml at 24 h, whereas at the same time points AZ concentrations remained below the limit of assay sensitivity (0.01 microgram/ml) for all but two subjects. The concentrations of CLA in the AM cells were significantly higher than those of AZ at 8 h (703 +/- 235 and 388 +/- 53 micrograms/ml, respectively). However, the ratio of the concentration in AM cells/concentration in plasma was significantly higher for AZ than for CLA for all time points because of the lower concentration of AZ in plasma. These results indicate that while AZ has higher tissue concentration to plasma ratios, as shown by other investigators, the absolute concentrations of CLA in AM cells and ELF are higher for up to 8 and 12 h, respectively, after administration of the last dose.

scholarly journals Pulmonary Disposition of Tedizolid following Administration of Once-Daily Oral 200-Milligram Tedizolid Phosphate in Healthy Adult Volunteers

2012 ◽  
Vol 56 (5) ◽  
pp. 2627-2634 ◽  
Author(s):  
Seth T. Housman ◽  
J. Samuel Pope ◽  
John Russomanno ◽  
Edward Salerno ◽  
Eric Shore ◽  
...  
Keyword(s):  
Correction Method ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Epithelial Lining Fluid ◽  
Once Daily ◽  
Dosing Interval ◽  
Drug Concentrations ◽  
Liquid Chromatography Tandem Mass ◽  
Adult Volunteers

ABSTRACTThis study assessed the pulmonary disposition of tedizolid, an oxazolidinone, in adult volunteers receiving 200 mg of the prodrug tedizolid phosphate orally every 24 h for 3 days to steady state. Plasma samples were collected over the dosing interval, and participants were randomized to undergo bronchoalveolar lavage (BAL) at 2, 6, 12, or 24 h after the last dose. Drug concentrations in plasma, BAL fluid, and alveolar macrophages (AM) were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the urea correction method was used to calculate epithelial lining fluid (ELF) concentrations. Pharmacokinetic parameters were estimated by noncompartmental methods followed by compartmental population pharmacokinetics. Penetration was calculated as the area under the concentration-time curve during the dosing interval (AUC0–24) for ELF and AM relative to the free AUC0–24(fAUC0–24) in plasma. The half-life and volume of distribution in plasma were 9.23 ± 2.04 h and 108.25 ± 20.53 liters (means ± standard deviations), respectively. Total AUC0–24in plasma was 25.13 ± 5.78 μg · h/ml. Protein binding was 89.44% ± 1.58%, resulting in a meanfAUC0–24of 2.65 ± 0.72 μg · h/ml in plasma. Mean concentrations (μg/ml) at 2, 6, 12, and 24 h were 9.05 ± 3.83, 4.45 ± 2.18, 5.62 ± 1.99, and 1.33 ± 0.59 in ELF and 3.67 ± 1.02, 4.38 ± 2.18, 1.42 ± 0.63, and 1.04 ± 0.52 in AM. ELF and AM penetration ratios were 41.2 and 20.0. The mean ELF penetration ratio after population analyses was 39.7. This study demonstrates that tedizolid penetrates into ELF and AM to levels approximately 40-fold and 20-fold, respectively, higher than free-drug exposures in plasma.

Irrigation Volume, Application, and Controlled-release Fertilizer II. Effect on Substrate Solution Nutrient Concentration and Water Efficiency in Containerized Plant Production

1998 ◽  
Vol 16 (3) ◽  
pp. 182-188
Author(s):  
Kelly M. Groves ◽  
Stuart L. Warren ◽  
Ted E. Bilderback
Keyword(s):  
Controlled Release ◽  
Irrigation Efficiency ◽  
Plant Production ◽  
Water Efficiency ◽  
Solution Ph ◽  
Entire Study ◽  
Once Daily ◽  
Substrate Solution ◽  
Irrigation Volume ◽  
Controlled Release Fertilizers

Abstract Rooted cuttings of Cotoneaster dammeri Schneid ‘Skogholm’ and seedlings of Rudbeckia fulgida Ait. ‘Goldsturm’ were potted into 3.8 liter (4 qt) containers in a pine bark:sand (8:1 by vol) substrate incorporated with 3.5 g (0.12 oz) N per container provided by one of the following five controlled-release fertilizers (CRFs): Meister 21N–3.5P–11.1K (21–7–14), Osmocote 24N–2.0P–5.6K (24–4–7), Scotts 23N–2.0P–6.4K (23–4–8), Sustane 5N–0.9P–3.3K (5–2–4) or Woodace 21N–3.0P–9.5K (21–6–12). Two hundred ml (0.3 in), 400 ml (0.6 in), 800 ml (1.1 in) or 1200 ml (1.7 in) of water was applied once daily (single) or in two equal applications with a 2 hr interval between applications (cyclic). Substrate solutions were collected from containers of cotoneaster 15, 32, 45, 60, 74, 90, 105, and 119 days after initiation (DAI). Irrigation efficiency [(water applied − water leached) ÷ water applied] was determined on the same days. Cyclic application improved irrigation efficiency at 800 ml (1.1 in) and 1200 ml (1.7 in) ≈ 27% compared to a single application. Irrigation efficiencies averaged over the season were 95%, 84%, 62%, and 48% for cotoneaster and 100%, 90%, 72%, and 51% for rudbeckia at 200 ml (0.3 in), 400 ml (0.6 in), 800 ml (1.1 in) and 1200 ml (1.7 in), respectively. NH4-N and NO3-N and PO4-P concentrations in substrate solution decreased with increasing irrigation volume regardless of CRF. Substrate NH4-N concentration decreased throughout the season with most CRFs below 5 mg/liter by 90 DAI. CRFs mainly affected substrate NH4-N and NO3-N concentrations when irrigated with 200 ml (0.3 in) or 400 ml (0.6 in). Substrate NH4-N, NO3-N, and PO4-P solution concentrations were similar for all CRFs at irrigation volume of 1200 ml (1.7 in). Osmocote, Scotts, and Woodace maintained relatively constant substrate solution levels of PO4-P through 60 DAI. By 90 DAI, substrate PO4-P levels were similar regardless of irrigation volume or CRF. Substrate PO4-P concentrations were never in the recommended range of 5 to 10 mg/liter when irrigated with 800 ml (1.1 in) or 1200 ml (1.7 in) regardless of CRF. Solution pH remained in the recommended range of 5.0 to 6.0 for all irrigation volumes and CRFs throughout the entire study with the exception of Sustane.

Comparative study of Clinical Characteristics in Patients with Mild and Severe Reflux Esophagitis

2020 ◽  
Vol 66 (1) ◽  
pp. 19-22
Author(s):  
Melania Macarie ◽  
Simona Maria Bataga ◽  
Monica Pantea ◽  
Razvan Opaschi ◽  
Simona Mocan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sex Ratio ◽  
Hiatal Hernia ◽  
Statistical Significance ◽  
Erosive Esophagitis ◽  
Male Gender ◽  
Consecutive Series ◽  
Study Group ◽  
Entire Study ◽  
Significant Difference

AbstractObjective: This study aims to determine the correlation between risk factors and erosive esophagitis development.Methods: We conducted a retrospective observational study on a consecutive series of 19.672 patients who underwent upper gastrointestinal endoscopy between 01.01.2011-31.12.2017. A total of 3005 patients, diagnosed with erosive esophagitis, were included in the present study and stratified according to Los Angeles classification.Results: During the studied period we found 3005 patients with erosive esophagitis, sex ratio male to female was 1.3/1, the most common forms of esophagitis being grade A and B: 74.54% patients with esophagitis grade A, 14.80% patients with grade B; 5.29% patients were with grade C and 5.35% patients with esophagitis grade D. In severe esophagitis the male predominance was more prevalent (249 males, 71 female), with a sex ratio 3.50/1. The correlation of male gender with severe esophagitis was highly statistically significant (p < 0.0001, OR 2.97; 95% CI 2.25-3.91). Hiatal hernia was diagnosed in 1171 patients, the presence of large hiatal hernias, being an important predictor, with statistical significance (p < 0.0001, OR 3.41; 95% CI 2.22-5.21), for severe esophagitis development. Incidence of Helicobacter pylori infection was 11.51%, in the entire study group, with no statistical significant difference between patients with mild or severe esophagitis (12.02% vs 7.18%).Conclusion: Erosive esophagitis is a frequent disease, the most common forms being grade A and B. Male gender and the presence of hiatal hernia are the most important risk factors for erosive esophagitis development, in our study group.

Follow-up of the Isolated Medial Approach to Hallux Abducto Valgus Correction Without Interspace Release

2002 ◽  
Vol 92 (10) ◽  
pp. 555-562 ◽  
Author(s):  
Jeffrey S. Boberg ◽  
Molly S. Judge
Keyword(s):  
Metatarsophalangeal Joint ◽  
Valgus Deformity ◽  
Study Group ◽  
Entire Study ◽  
First Metatarsophalangeal Joint ◽  
Intermetatarsal Angle ◽  
Medial Approach ◽  
Average Decrease ◽  
First Ray

A retrospective radiographic review was performed of 29 patients (37 feet) who underwent an isolated medial approach for correction of hallux abducto valgus deformity from March 1993 to November 1998. Only those patients who had a traditional Austin-type osteotomy with a reducible first metatarsophalangeal joint and flexible first ray were included in the study. The average follow-up period for the entire study group was 18.4 months, with 13 patients (44.83%; 17 feet) having a follow-up period of longer than 2 years. The average decrease in the intermetatarsal angle was 9.89°, and the average decrease in the hallux abductus angle was 14.0°, results that correlated well with those of other studies on correction of hallux abducto valgus. No clinical or radiographic recurrence of hallux abducto valgus was noted throughout the follow-up period. The authors believe that an isolated medial approach to hallux abducto valgus correction without a lateral interspace release yields predictable results when performed in appropriately selected patients. (J Am Podiatr Med Assoc 92(10): 555-562, 2002)

Letters to the Editor

PEDIATRICS ◽  
1980 ◽  
Vol 66 (6) ◽  
pp. 1033-1034
Author(s):  
M. De Swiet ◽  
E. A. Shinebourne ◽  
P. M. Fayers
Keyword(s):  
Blood Pressure ◽  
Study Group ◽  
Letters To The Editor ◽  
Entire Study ◽  
Blood Pressures

We agree with Dr Gillum that omission of some of the readings made at ages 6 months and 1 year could have produced bias in the results that we have quoted for blood pressure at these ages. However, the 5-cm cuff whose results were omitted was one of the middle sized cuffs and therefore the weights of the infants whose blood pressures were omitted were in the middle of the distribution at each age. As the Table shows, their blood pressures when measured on other occasions were also not significantly different from the blood pressures of the entire study group.

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