An Open, Randomised, Single Dose, 2-period, 2-sequence Crossover Adhesion Study of Two Different Transdermal Patches Containing Rotigotine.

2019 ◽  
Author(s):  
Keyword(s):  
Single Dose ◽  
Transdermal Patches ◽  
Period 2

Relative bioavailability (BA) and bioequivalence (BE) study of abiraterone acetate (AA) fine particle (AAFP) with methylprednisolone (MP) and a reference formulation with prednisone (PN) in healthy male subjects.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16538-e16538
Author(s):  
Azra Hussaini ◽  
Anthony J. Olszanski ◽  
Cy Aaron Stein ◽  
Bill Bosch ◽  
Paul Nemeth
Keyword(s):  
Single Dose ◽  
Fine Particle ◽  
Drug Exposure ◽  
Geometric Mean ◽  
Relative Bioavailability ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Fasted State ◽  
Period 2

e16538 Background: AA is approved for treatment of metastatic castration-resistant prostate cancer when taken in combination with PN. The originator AA (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic (PK) variability. AAFP is a proprietary formulation (utilizing SoluMatrix Fine-Particle Technology™) that was designed to provide improved BA. In a prior study in healthy subjects, AAFP 500 mg was established as bioequivalent to OAA 1000 mg when given in the fasted state. In this study, AAFP was evaluated in subjects in a fasted state with steady state (SS) MP, an alternative steroid to PN. Methods: Subjects aged 18–50 years were randomized in a crossover design to receive MP (4 mg BID) or PN (5 mg BID) for 12 days in Period 1. On Day 11 of Period 1, subjects given MP received a single dose of AAFP 500 mg (test) and subjects given PN received a single dose of OAA 1000 mg (reference). After a 2-week steroid washout period, subjects received the alternate treatments in Period 2. Results: There were no statistical differences with regard to abiraterone AUC ( P≥0.38) and Cmax ( P= 0.22) between AAFP 500 mg and OAA 1000 mg (Table). Geometric mean ratio (GMR), a measure of BE, was 95.9% (90% CI: 86.0–106.9%) for AUC0-∞, 99.2% (90% CI: 88.7–110.9%) for AUC0-t, and 116.8% (90% CI: 102.2–133.4%) for Cmax. GMR of AUC0-∞ and AUC0-t, fell within the 80–125% range for BE, and Cmax 90% CI was just outside the upper limit. The coefficient of variance (CV) for both AUC and Cmaxwas smaller for AAFP compared with OAA. Both treatments were safe and well tolerated. Conclusions: AAFP 500 mg with MP gave comparable exposure to OAA 1000 mg with PN with respect to Cmaxand AUC. Less drug exposure variability was observed with AAFP compared with OAA. Reduced PK variability could improve clinical outcomes and warrants further study. [Table: see text]

scholarly journals Evaluation of the Pharmacokinetic Interaction between Repeated Doses of Rifapentine or Rifampin and a Single Dose of Bedaquiline in Healthy Adult Subjects

2014 ◽  
Vol 59 (2) ◽  
pp. 1219-1224 ◽  
Author(s):  
Helen Winter ◽  
Erica Egizi ◽  
Stephen Murray ◽  
Ngozi Erondu ◽  
Ann Ginsberg ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Adult ◽  
Geometric Mean ◽  
Pharmacokinetic Interaction ◽  
Time Curve ◽  
Concentration Time ◽  
Period 2 ◽  
Repeated Doses ◽  
Single Sequence ◽  
Time Point

ABSTRACTThis study assessed the effects of rifapentine or rifampin on the pharmacokinetics of a single dose of bedaquiline and its M2 metabolite in healthy subjects using a two-period single-sequence design. In period 1, subjects received a single dose of bedaquiline (400 mg), followed by a 28-day washout. In period 2, subjects received either rifapentine (600 mg) or rifampin (600 mg) from day 20 to day 41, as well as a single bedaquiline dose (400 mg) on day 29. The pharmacokinetic profiles of bedaquiline and M2 were compared over 336 h after the administration of bedaquiline alone and in combination with steady-state rifapentine or rifampin. Coadministration of bedaquiline with rifapentine or rifampin resulted in lower bedaquiline exposures. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for the maximum observed concentration (Cmax), area under the concentration-time curve to the last available concentration time point (AUC0–t), and AUC extrapolated to infinity (AUC0–inf) of bedaquiline were 62.19% (53.37 to 72.47), 42.79% (37.77 to 48.49), and 44.52% (40.12 to 49.39), respectively, when coadministered with rifapentine. Similarly, the GMRs and 90% CIs for theCmax, AUC0–t, and AUC0–infof bedaquiline were 60.24% (51.96 to 69.84), 41.36% (37.70 to 45.36), and 47.32% (41.49 to 53.97), respectively, when coadministered with rifampin. TheCmax, AUC0–t, and AUC0–infof M2 were also altered when bedaquiline was coadministered with rifapentine or rifampin. Single doses of bedaquiline, administered alone or with multiple doses of rifapentine or rifampin, were well tolerated, with no safety concerns related to coadministration. Daily administration of rifapentine to patients with tuberculosis presents the same drug interaction challenges as rifampin and other rifamycins. Strong inducers of the cytochrome P450 isoenzyme CYP3A4 should be avoided when considering the use of bedaquiline. (This study is registered at clinicaltrials.gov under identifier NCT02216331.)

Bioequivalence of Lamotrigine 50-mg Tablets in Healthy Male Volunteers: a Randomized, Single-Dose, 2-Period, 2-Sequence Crossover Study

2012 ◽  
Vol 62 (10) ◽  
pp. 470-476 ◽  
Author(s):  
S. Perez-Lloret ◽  
L. Olmos ◽  
F. de Mena ◽  
P. Pieczanski ◽  
J. Rodriguez Moncalvo
Keyword(s):  
Single Dose ◽  
Crossover Study ◽  
Healthy Male ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
Period 2

Pharmacokinetic Comparison of 2 Formulations of Anastrozole (1 mg) in Healthy Korean Male Volunteers: A Randomized, Single-Dose, 2-Period, 2-Sequence, Crossover Study

2012 ◽  
Vol 34 (2) ◽  
pp. 305-313 ◽  
Author(s):  
Yook-Hwan Noh ◽  
Young-Ju Ko ◽  
Sang-Heon Cho ◽  
Jong-Lyul Ghim ◽  
Sangmin Choe ◽  
...  
Keyword(s):  
Single Dose ◽  
Crossover Study ◽  
Male Volunteers ◽  
Period 2

scholarly journals Pharmacokinetics and Bioequivalence of Isavuconazole Administered as Isavuconazonium Sulfate Intravenous Solution via Nasogastric Tube or Orally in Healthy Subjects

2021 ◽  
Author(s):  
Amit Desai ◽  
Melanie Helmick ◽  
Nakyo Hoe ◽  
Selina Moy ◽  
Stephen Stanhope ◽  
...  
Keyword(s):  
Single Dose ◽  
Oral Administration ◽  
Fungal Infections ◽  
Open Label ◽  
Serious Adverse Events ◽  
Time Curve ◽  
Mean Values ◽  
Routes Of Administration ◽  
Period 2 ◽  
Intravenous Solution

For critically ill patients with invasive fungal infections, administration of isavuconazonium sulfate (ISAVUSULF) via nasogastric (NG) tube can be an alternative route of drug administration. This was a randomized, open-label, 2-period, 2-sequence single-dose crossover study comparing single doses of 372 mg ISAVUSULF intravenous (IV) solution via NG tube (test formulation) to 372 mg ISAVUSULF capsules for oral administration (reference formulation) in healthy male and female subjects. A single dose of ISAVUSULF was administered under fasting conditions on Day 1 of each period, with a washout of 30 days between each period. Pharmacokinetic (PK) samples were collected predose through Day 21. Standard safety and tolerability assessments were conducted in each period. The analysis of variance estimate of the study population demonstrates that the isavuconazole IV NG tube administration Geometric least squares (LS) mean values of the observed maximum concentration (C max ), area under the plasma concentration–time curve (AUC) to the last measurable concentration (AUC last ), AUC to time infinity (AUC inf ), and AUC from start of dosing to 72 hours (AUC 72 ) were 105.3%, 97.6%, 99.3% and 97.8%, respectively, of the corresponding oral administration values. The Geometric LS mean ratio and 90% confidence intervals for the PK parameters were completely contained within the prespecified limits of 80% to 125%. There were no deaths or serious adverse events that led to the withdrawal of treatment during the study. The study met its primary endpoint of bioequivalence between the two routes of administration. Both routes of administration were well tolerated.

The Response of Testes Cells to Low Level, Single dose Helium Particle Irradiation

1982 ◽  
Vol 40 ◽  
pp. 252-253
Author(s):  
D.E. Philpott ◽  
W. Sapp ◽  
C. Williams ◽  
J. Stevenson ◽  
S. Black ◽  
...  
Keyword(s):  
Stem Cell ◽  
Single Dose ◽  
B Cell ◽  
Cell Survival ◽  
Spermatogonial Stem Cell ◽  
Low Doses ◽  
Particle Irradiation ◽  
Stem Cell Survival ◽  
Irradiation Injury ◽  
Radio Sensitivity

Spermatogonial stem-cell survival after irradiation injury has been studied in rodents by histological counts of surviving cells. Many studies, including previous work from our laboratory, show that the spermatogonial population demonstrates a heterogeneous response to irradiation. The spermatogonia increase in radio-sensitivity as differentiation proceeds through the sequence As - Apr - A1 - A2 - A3 - A4 - In - B. The stem (As) cell is the most resistant and the B cell is the most sensitive. The purpose of this work is to investigate the response of spermatogonial cell to low doses (less than 10 0 rads) of helium particle irradiation.

Gastric Ulcers Produced by Cisplatin

1981 ◽  
Vol 39 ◽  
pp. 582-583
Author(s):  
S.K. Aggarwal ◽  
J. San Antonio
Keyword(s):  
Electron Microscopy ◽  
Single Dose ◽  
Side Effects ◽  
Antitumor Agent ◽  
Gastric Ulcers ◽  
Enzyme Cytochemistry ◽  
Intestinal Toxicity ◽  
Ovarian Cancers ◽  
Inner Surface

Cisplatin (cis-dichlorodiammineplatinum(II)) a potent antitumor agent is now available for the treatment of testicular and ovarian cancers. It is however, not free from its serious side effects including nephrotoxicity, gastro intestinal toxicity, myelosuppression, and ototoxicity. Here we now report that the drug produces peculiar bloating of the stomach in rats and induces acute ulceration.Wistar-derived rats weighing 200-250 g were administered cisplatin(9 mg/kg) ip as a single dose in 0.15 M NaCl. After 3 days the animals were sacrificed by decapitation. The stomachs were removed, the contents analyzed for pepsin and acidity. The inner surface was examined with a dissecting microscope after a moderate stretching for ulcers. Affected areas were fixed and processed for routine electron microscopy and enzyme cytochemistry.The drug treated animals kept on food and water consistently showed bloating and lesions (Fig. 1) with a frequency of 6-70 ulcers in the rumen section of the stomachs.

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