scholarly journals The Comparative Evaluation of the Time to Peak Concentration and the Terminal Half-Life of Two Products Based on Praziquantel in a Bioequivalence Study

2015 ◽  
Vol 72 (1) ◽  
Author(s):  
Alexandra Georgiana Arion ◽  
Istvan Torok ◽  
Ferenc Nagy ◽  
Annamaria Imre ◽  
Francisc Andrei Boda ◽  
...  
Keyword(s):  
Half Life ◽  
Comparative Evaluation ◽  
Peak Concentration ◽  
Bioequivalence Study ◽  
Time To Peak ◽  
Terminal Half Life

Pharmacokinetic Considerations of Misonidazole in Therapeutics

1984 ◽  
Vol 3 (1) ◽  
pp. 29-36 ◽  
Author(s):  
I. Matheson ◽  
P.N. Plowman ◽  
A. Johnston
Keyword(s):  
Half Life ◽  
Peak Concentration ◽  
Optimal Timing ◽  
High Dose ◽  
Marked Variation ◽  
Time To Peak ◽  
Conventional Dose ◽  
Frequent Sampling

The pharmacokinetics of misonidazole have been studied in 6 patients with special emphasis on determination of the peak concentration in plasma and saliva. Frequent sampling was performed over 4 h and a marked variation in absorption half-life (range 4 - 125 min) and time to peak range (0.5 - 6.5 h) was found. The optimal timing of irradiation is discussed. In addition to a conventional dose, one of the patients received high dose misonidazole; the pharmacokinetics are compared.

Phase I Dose-Finding Study of Weekly Single-Agent Patupilone in Patients With Advanced Solid Tumors

2005 ◽  
Vol 23 (36) ◽  
pp. 9120-9129 ◽  
Author(s):  
Eric H. Rubin ◽  
John Rothermel ◽  
Fisseha Tesfaye ◽  
Tianling Chen ◽  
Martine Hubert ◽  
...  
Keyword(s):  
Partial Response ◽  
Solid Tumors ◽  
Half Life ◽  
Drug Exposure ◽  
Dose Range ◽  
Single Agent ◽  
Dose Finding ◽  
Advanced Solid Tumors ◽  
Blood Concentrations ◽  
Terminal Half Life

Purpose To evaluate the safety and maximum-tolerated dose (MTD) of weekly patupilone, a natural epothilone B, in patients with advanced solid tumors. Patients and Methods Patients were treated with patupilone (0.3 to 3.6 mg/m2) for 6 weeks on/3 weeks off or 3 weeks on/1 week off. Dose-limiting toxicities (DLTs), MTD, and pharmacokinetics were determined for each schedule of administration. Results Ninety-one patients were enrolled. The most common tumor types included ovarian, breast, and colon cancers. Doses of patupilone less than 2.5 mg/m2 using either the 6 weeks on/3 weeks off or the 3 weeks on/1 week off schedule were tolerated well. At higher doses, DLTs were observed using both dosing schedules, with diarrhea the most common DLT. The MTD for both treatment schedules was 2.5 mg/m2. After a short infusion, patupilone blood concentrations declined in a multiphasic manner with a terminal half-life of 4 days. Drug clearance was nonrenal and was not related to body-surface area. Over the dose range evaluated, systemic drug exposure was approximately dose proportional. Three patients achieved a partial response, and 31 patients had stable disease. Two patients experiencing a partial response had received prior taxane therapy. Conclusion Patupilone is well tolerated when administered at a dose of 2.5 mg/m2, using either a 6 weeks on/3 weeks off or a 3 weeks on/1 week off schedule. In contrast with murine studies, patupilone has a relatively prolonged terminal half-life in humans. The partial responses in patients previously treated with taxanes is consistent with promising preclinical results.

scholarly journals hCGbeta core fragment is a metabolite of hCG: evidence from infusion of recombinant hCG

2000 ◽  
Vol 164 (3) ◽  
pp. 299-305 ◽  
Author(s):  
RJ Norman ◽  
MM Buchholz ◽  
AA Somogyi ◽  
F Amato
Keyword(s):  
Renal Clearance ◽  
Clearance Rate ◽  
Half Life ◽  
Urine Samples ◽  
Molar Ratio ◽  
Gel Chromatography ◽  
Core Fragment ◽  
Terminal Half Life ◽  
Intact Molecule ◽  
The Mean

The availability of recombinant human chorionic gonadotrophin (r-hCG) has allowed us to measure its metabolic and renal clearance rates and to study the origin of the beta core fragment of hCG (hCGbetacf). Serum and urine samples were collected from six subjects, after an intravenous injection of 2 mg (equivalent to 44 000 IU Urinary hCG) r-hCG, and assayed for hCG and the beta subunit (hCGbeta). Urine from four of the subjects was also subjected to gel chromatography and assayed for hCGbetacf and hCG. r-hCG, administered as an intravenous dose, was distributed, initially in a volume of 3.4+/-0.7 l (mean+/-s.d.) and then in 6.5+/-1.15 l at steady-state. The disappearance of r-hCG from serum was bi-exponential, with an initial half-life of 4.5+/-0.7 h and a terminal half-life of 29.0+/-4.6 h. The mean residence time was 28. 6+/- 3.6 h and the total systemic clearance rate of r-hCG was 226+/-18 ml/h. The renal clearance rate was 28.75+/-6.2 ml/h (mean+/-s.d). hCGbetacf was detected in all urine samples collected at 6 h intervals. Over the 138 h period of urine collection, 12.9% (range 10.1-17.3% ) of r-hCG injected was recovered as the intact molecule and 1.7% (range 0.8-2.9%) was recovered as the hCGbetacf, in 4 subjects. The molar ratio of hCGbetacf to hCG in urine increased from 3.1+/-1.7%, on day 1, to 76+/-34.3% (mean+/-s.e.m.) on day 5, after r-hCG infusion, suggesting that hCGbetacf is a metabolic product of the infused r-hCG.

Human biokinetics of injected bismuth-207

2001 ◽  
Vol 20 (12) ◽  
pp. 601-609 ◽  
Author(s):  
D Newton ◽  
R J Talbot ◽  
N D Priest
Keyword(s):  
Half Life ◽  
Male Volunteer ◽  
Healthy Male Volunteer ◽  
Metabolic Model ◽  
The Body ◽  
Whole Body ◽  
Radiological Protection ◽  
Bismuth Compounds ◽  
Terminal Half Life ◽  
Radioactivity Measurements

A healthy male volunteer received an intravenous injection of 207Bi as citrate. Levels of the tracer in blood and in excretion samples, and its retention and distribution within the body, were investigated by appropriate radioactivity measurements. Levels in blood fell very rapidly, with only 1% of the injection remaining at 7 h and only ca. 0.1% at 18 days. There was rapid initial excretion, with 55% lost during the first 47 h, principally in urine; however, longer-term losses were much slower and 0.6% remained in the body at 924 days, when the contemporary rate of loss implied a half-life of 1.9 years. Integration of the retention pattern suggested that steady exposure to bismuth compounds could lead ultimately to a body content of 24 times the daily systemic uptake. The largest organ deposit was in the liver, which after 3 days contained ca. 60% of the contemporary whole body content, consistent with reports of hepatotoxicity. These findings differ markedly from the metabolic model for bismuth proposed by the International Commission on Radiological Protection, which envisages a terminal half-life in the body of only 5 days and kidney as the site of highest deposition.

scholarly journals Use of a rapid HPLC assay for determination of pharmacokinetic parameters of ibuprofen in patients with cystic fibrosis

1996 ◽  
Vol 42 (11) ◽  
pp. 1812-1816 ◽  
Author(s):  
N Rifai ◽  
M Sakamoto ◽  
T Law ◽  
V Galpchian ◽  
N Harris ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Adverse Effects ◽  
Peak Concentration ◽  
Therapeutic Monitoring ◽  
Pharmacokinetic Parameters ◽  
Hplc Assay ◽  
Average Recovery ◽  
Time To Peak ◽  
High Doses

Abstract High doses of ibuprofen have been shown to delay the progression of lung disease without serious adverse effects in patients with cystic fibrosis. To be effective, peak ibuprofen concentration of 50 to 100 mg/L has to be achieved. We developed an HPLC assay to rapidly determine plasma ibuprofen concentration. We used this assay to determine the pharmacokinetics of ibuprofen in patients with cystic fibrosis. The assay possessed linearity up to 500 mg/L, sensitivity to 1 mg/L, average recovery of 98%, and run-to-run precision (n = 23) of 3%. Furthermore, the assay proved to be free of interference from 51 medications. Observed time to peak concentration varied significantly between those receiving ibuprofen tablets (mean + SD, 94 +/- 29 min, n = 16) and syrup (30 +/- 0 min, n = 4) (P < 0.0001). We conclude that the method described here is ideal for therapeutic monitoring of ibuprofen.

scholarly journals Levers to Improve Antibiotic Treatment of Lambs via Drinking Water in Sheep Fattening Houses: The Example of the Sulfadimethoxine/Trimethoprim Combination

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 561
Author(s):  
Aude A. Ferran ◽  
Marlène Z. Lacroix ◽  
Alain Bousquet-Mélou ◽  
Ivain Duhil ◽  
Béatrice B. Roques
Keyword(s):  
Drinking Water ◽  
Oral Bioavailability ◽  
Half Life ◽  
Plasma Concentrations ◽  
Oral Route ◽  
Disease Spread ◽  
Bacterial Diseases ◽  
Terminal Half Life ◽  
High Interindividual Variability ◽  
The Individual

To limit the spread of bacterial diseases in sheep fattening houses, antibiotics are often administered collectively. Collective treatments can be delivered by drinking water but data on the drug’s solubility in water or on plasma exposure of the animals are lacking. We first assessed the solubility of products containing sulfadimethoxine (SDM), associated or not with trimethoprim (TMP), in different waters. We then compared in lambs the SDM and TMP pharmacokinetic profiles after individual intravenous (IV) and oral administrations of SDM-TMP in experimental settings (n = 8) and after a collective treatment by drinking water with SDM-TMP or SDM alone in a sheep fattening house (n = 100 for each treatment). The individual water consumption during the collective treatments was also monitored to characterize the ingestion variability. We showed that TMP had a short terminal half-life and very low oral bioavailability, demonstrating that it would be unable to potentiate SDM by oral route. Conversely, SDM had a long terminal half-life of 18 h and excellent oral bioavailability. However, delivery by drinking water resulted in a very high interindividual variability of SDM plasma concentrations, meaning that although disease spread could be controlled at the group level, some individuals would inevitably be under- or over-exposed to the antibiotic.

scholarly journals 81 Bioequivalence of a Manipulation-Resistant Immediate-Release Amphetamine Sulfate Formulation Compared with Reference Standard

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 216-216
Author(s):  
Steve Caras ◽  
Terrilyn Sharpe
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Peak Concentration ◽  
Immediate Release ◽  
Open Label ◽  
Time Curve ◽  
Time To Peak ◽  
Amphetamine Sulfate ◽  
Quantifiable Concentration ◽  
Funding Acknowledgements

AbstractStudy ObjectivesWe compared the bioavailability of racemic amphetamine (d-amphetamine and l-amphetamine) from a manipulation-resistant immediate-release (IR) amphetamine sulfate capsule (AR19) versus amphetamine sulfate IR tablets (reference).MethodIn this open-label, randomized, two-period, two-treatment, two-sequence, crossover study, 36 healthy volunteers aged 18–45 received a single dose (20-mg capsule) of AR19 in one period and a single dose (2 x 10-mg tablets) of reference in another period, after a 10-hour overnight fast. Each drug administration was separated by a washout period of at least 6days. Bioequivalence for d- and l-amphetamine was assessed using time to peak concentration (Tmax), peak concentration in plasma (Cmax), and area under the plasma concentration–time curve from time-zero to the time of the last quantifiable concentration (AUClast) and extrapolated to infinity (AUCinf).ResultsAll 36 volunteers completed both treatment sequences. Mean (standard deviation; SD) Tmax for d- and l-amphetamine was similar for AR19 (2.84[1.05]; 3.05[1.22], respectively) and reference (2.52[0.75]; 2.75[1.00], respectively). The geometric least-squares mean ratios and 90% confidence intervals were within the boundary of 80%–125% for bioequivalence for Cmax (d-amphetamine, 98.35% [96.12–100.64]; l-amphetamine, 98.82% [96.42–101.28]), AUClast (d-amphetamine, 99.45% [96.92–102.05]; l-amphetamine, 99.29% [96.55–102.10]), and AUCinf (d-amphetamine, 99.50%[96.77–102.30]; l-amphetamine, 99.23% [96.06–102.50]). A total of 13 mild adverse events were reported by 7 volunteers (AEs; AR19, n=5; reference, n=8). No serious AEs were reported.ConclusionAR19 was well tolerated and was bioequivalent to reference when administered as a 20-mg dose in healthy volunteers.Funding Acknowledgements: This study was funded by Arbor Pharmaceuticals, LLC.

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