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Clinical Pharmacology in Drug Development

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https://www.readbyqxmd.com/read/28176487/lornoxicam-immediate-release-tablets-formulation-and-bioequivalence-study-in-healthy-mediterranean-volunteers-using-a-validated-lc-ms-ms-method
#1
Abdel Naser Zaid, Ayman Mousa, Nidal Jaradat, Rana Bustami
This study aimed to demonstrate interchangeability between 2 lornoxicam tablet formulations under fasting conditions among Mediterranean Arabs by using a newly validated high-pressure liquid chromatography-tandem mass spectrometry method. A single-oral solid dosage form (8 mg/tablet), randomized, open-label, 2-way crossover study was conducted on 30 healthy male volunteers. Blood samples were collected prior to dosing and over a 24-hour period, and the washout period was 9 days. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between generic and branded products...
February 8, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28176470/effect-of-sustained-elevated-gastric-ph-levels-on-gefitinib-exposure
#2
Weifeng Tang, Helen Tomkinson, Eric Masson
This open-label, randomized, phase 1 crossover study investigated the effect of elevated gastric pH level (>5) on the relative bioavailability and pharmacokinetic profile of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib. Healthy male volunteers (n = 26) were randomized to gefitinib 250 mg (fasted), either alone on day 1 (unmodified gastric pH) or 1 hour following the second of 2 oral doses of the H2 -receptor antagonist ranitidine 450 mg (elevated gastric pH). After a 3-week washout period, volunteers crossed to the other treatment...
February 8, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28168828/relative-bioavailability-of-a-dolutegravir-dispersible-tablet-and-the-effects-of-low-and-high-mineral-content-water-on-the-tablet-in-healthy-adults
#3
Ann M Buchanan, Michael Holton, Ian Conn, Mark Davies, Mike Choukour, Brian R Wynne
Dolutegravir (DTG) is approved in the United States to treat HIV-1-infected patients weighing ≥30 kg. A dispersible DTG tablet formulation was recently developed for pediatric patients. This study compares the pharmacokinetics (PK) of the dispersible tablet with that of a previously evaluated granule formulation. In this randomized, open-label, crossover study, 15 healthy adults received single oral doses of DTG 20 mg every 7 days across 5 treatment arms: granules consumed immediately after mixture with purified water, dispersible DTG consumed immediately after reconstitution in low-mineral-content (LMC) or high-mineral-content (HMC) water, and dispersible DTG consumed 30 minutes after dispersal in LMC or HMC water...
February 7, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28127948/bioequivalence-studies-of-a-reformulated-dutasteride-and-tamsulosin-hydrochloride-combination-capsule-and-a-commercially-available-formulation
#4
Renee Kurczewski, Chet Bowen, David Collins, John Zhu, Gulyeter Serbest, Michael Manyak
A dutasteride 0.5 mg and tamsulosin hydrochloride 0.4 mg combination (DTC) capsule (Duodart(®) ) was reformulated to reduce the capsule size and enhance product stability. Bioequivalence of the reformulated DTC capsule with the commercial formulation was evaluated in 2 single-dose, open-label, randomized, 2-way crossover studies in healthy adult male volunteers. Subjects in a fasted or fed state received a single oral dose of either the reformulated DTC or the commercial formulation followed by a 28-day washout period between treatments...
January 27, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28127938/an-open-label-randomized-bioavailability-study-of-alternative-methods-of-oral-administration-of-naloxegol-in-healthy-subjects
#5
Khanh Bui, Bruce Birmingham, Ulysses Diva, Bruce Berger
Naloxegol is a peripherally acting μ-opioid receptor antagonist approved as an orally administered tablet for the treatment of opioid-induced constipation. Patients with swallowing difficulties may benefit from alternative approaches to the oral administration of the whole-tablet formulation of naloxegol. This open-label, randomized, 4-period, 4-treatment, crossover, single-dose study (NCT02446171) evaluated the pharmacokinetic (PK) characteristics of crushed naloxegol 25-mg tablets (suspended in water) administered orally or by nasogastric tube and a naloxegol solution compared with the commercially available 25-mg tablet formulation in healthy volunteers...
January 27, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28111929/acid-inhibitory-effect-of-a-combination-of-omeprazole-and-sodium-bicarbonate-cdfr0209-compared-with-delayed-release-omeprazole-40%C3%A2-mg-alone-in-healthy-adult-male-subjects
#6
Kyu-Nam Kim, Sung-Won Yang, Hyunil Kim, Seong Shin Kwak, Young-Sang Kim, Doo-Yeoun Cho
CDFR0209, a combination of an immediate-release formulation of omeprazole 40 mg and sodium bicarbonate 1100 mg, has been developed to treat acid-related disorders. We compared the acid inhibitory effects of CDFR0209 and delayed-release omeprazole (omeprazole-DR, Losec 40 mg) after repeated dosing in Helicobacter pylori-negative healthy adult male subjects. In this 2-period crossover study, 30 subjects were randomized to CDFR0209 or omeprazole-DR daily for 7 days. An ambulatory continuous 24-hour intragastric pH recording was performed at baseline and on days 1 and 7 of each administration period...
January 23, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28074640/evaluation-of-pharmacokinetic-interactions-between-lesinurad-a-new-selective-urate-reabsorption-inhibitor-and-commonly-used-drugs-for-gout-treatment
#7
Zancong Shen, Kathy Tieu, David Wilson, Gail Bucci, Michael Gillen, Caroline Lee, Bradley Kerr
Lesinurad is a novel selective uric acid reabsorption inhibitor approved for treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors (XOIs). Open-label pharmacokinetic studies were performed in volunteers or subjects with hyperuricemia (serum uric acid ≥ 8 mg/dL) to investigate interactions of lesinurad (with and without concurrent XOIs) with colchicine and 2 nonsteroidal anti-inflammatory drugs: naproxen and indomethacin. Colchicine studies included consecutive 7-day treatment periods of (1) allopurinol 300 mg, allopurinol 300 mg plus lesinurad 400 or 600 mg, and continued lesinurad 400 or 600 mg; or (2) febuxostat 40 or 80 mg, febuxostat 40 or 80 mg plus lesinurad 400 mg, and continued febuxostat 40 or 80 mg plus lesinurad 600 mg...
January 11, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28067999/evaluation-of-pharmacokinetic-interactions-between-lesinurad-a-new-selective-urate-reabsorption-inhibitor-and-cyp-enzyme-substrates-sildenafil-amlodipine-tolbutamide-and-repaglinide
#8
Michael Gillen, Chun Yang, David Wilson, Shakti Valdez, Caroline Lee, Bradley Kerr, Zancong Shen
Lesinurad is a selective uric acid reabsorption inhibitor approved for the treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors. In vitro assays indicate that lesinurad is an inducer of CYPs in the order CYP3A > CYP2C8 > CYP2C9 > CYP2C19 > CYP2B6 and an inhibitor of CYP2C8 and CYP2C9. To investigate the drug interaction potential of lesinurad, clinical drug interaction studies were conducted. Open-label studies in volunteers investigated the effects of single-/multiple-dose lesinurad on the pharmacokinetics of sildenafil and amlodipine (CYP3A4 induction), tolbutamide (CYP2C9 inhibition/induction), and repaglinide (CYP2C8 inhibition/induction)...
January 9, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28052588/absolute-bioavailability-and-pharmacokinetic-comparability-of-sirukumab-following-subcutaneous-administration-by-a-prefilled-syringe-or-an-autoinjector
#9
Y Zhuang, D E de Vries, S J Marciniak, H Liu, H Zhou, H M Davis, F Leon, D Raible, Z Xu
This phase 1, randomized, open-label study assessed the absolute bioavailability and pharmacokinetic comparability of sirukumab, a human anti-interleukin-6 monoclonal antibody, following subcutaneous (SC) administration via Prefilled Syringe-UltraSafe Passive® Delivery System (PFS-U) or Prefilled Syringe-SmartJect® Autoinjector (PFS-AI; Janssen Research & Development, LLC, Spring House, Pennsylvania). A total of 144 healthy male subjects were randomized to 5 single-dose treatment groups: sirukumab 50 mg and 100 mg (each by PFS-U and PFS-AI) and sirukumab 100 mg intravenous (IV) infusion...
January 3, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28032482/population-pharmacokinetics-of-edoxaban-in-japanese-atrial-fibrillation-patients-with-severe-renal-impairment
#10
Takako Shimizu, Masaya Tachibana, Tetsuya Kimura, Tomohiko Kumakura, Kazutaka Yoshihara
This is a population pharmacokinetic (PopPK) analysis to predict PK of edoxaban, a direct-acting oral anticoagulant, in nonvalvular atrial fibrillation (NVAF) patients with severe renal impairment (SRI; creatinine clearance [CLcr ] <30 mL/min). Data from a phase 3 study recently conducted in Japanese NVAF patients (n = 90), including patients with SRI, were used to update the ENGAGE PopPK model that had been developed based on pooled data from the phase 3 ENGAGE AF-TIMI 48 study and 13 phase 1 PK studies, which included few patients with SRI...
December 29, 2016: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28032481/safety-tolerability-and-antihypertensive-effect-of-ser100-an-opiate-receptor-like-1-orl-1-partial-agonist-in-patients-with-isolated-systolic-hypertension
#11
Ilkka Kantola, Mika Scheinin, Trygve Gulbrandsen, Nils Meland, Knut T Smerud
The purpose of the present trial was to evaluate safety, tolerability, and effect on systolic blood pressure (SBP) of SER100 in a small group of patients with isolated systolic hypertension (ISH) in treatment with at least 1 antihypertensive drug. Eligible patients were randomized to either SER100 (10 mg) or placebo in a crossover design, and 2 doses were given subcutaneously (SC), 8 hours apart, on 2 consecutive days. On all treatment days patients were monitored with an ambulatory blood pressure measurement device for 12 daytime hours...
December 29, 2016: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28099796/a-fixed-dose-combination-of-bisoprolol-and-amlodipine-for-hypertension-a-potential-benefit-to-selected-patients
#12
EDITORIAL
Brian J Cohen
No abstract text is available yet for this article.
January 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27653022/management-of-hypertension-with-a-fixed-dose-single-pill-combination-of-bisoprolol-and-amlodipine
#13
REVIEW
Ulrike Gottwald-Hostalek, Ningling Sun, Christian Barho, Steven Hildemann
Hypertension is currently one of the greatest global health care challenges. Although many effective drugs are available, combinations of 2 or more medications are often required to meet clinical targets. Combination therapy has several advantages over monotherapy: lower doses of each drug can be used to achieve therapeutic goals; lower doses may lead to fewer adverse events, facilitating patient adherence; and using multiple drugs with different modes of action may be more effective in treating multifactorial diseases, including hypertension...
January 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27364900/single-and-multiple-dose-pharmacokinetics-of-immediate-release-extended-release-ibuprofen-tablets
#14
Thomas Legg, Edward Paluch, Shyamalie Jayawardena
A single-dose, randomized, open-label, crossover study (study 1; n = 35) and a multiple-dose, randomized, open-label, crossover study (study 2; n = 28) compared the pharmacokinetics of a new immediate-release/extended-release (IR/ER) bilayer tablet formulation of ibuprofen 600 mg every 12 hours with standard ibuprofen 200 mg IR every 4 hours. In both studies, the 2 formulations were bioequivalent to each other for the area under the plasma concentration-versus-time curve from time 0 to the last measurable concentration (AUCL), to infinity (AUC∞ ), and to 12 hours (AUC0-12 ) and maximum concentration (Cmax )...
January 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27297519/pharmacokinetics-of-lidocaine-and-its-metabolites-following-vaginal-administration-of-lidocaine-gel-to-healthy-female-subjects
#15
Bridget Martell, Harvey Kushner, Elaine Richardson, Amy Mize, Philip Mayer
Lidocaine vaginal bioadhesive gel is being developed as a local anesthetic for use in minimally invasive outpatient gynecological procedures and was investigated in single-dose and multiple-dose studies in healthy young adult women. Lidocaine doses of 2.5%, 5%, and 10% (w/w) were administered, and parent drug and metabolites monoethylglycinexylidide and glycinexylidide were measured in plasma. Lidocaine was absorbed through vaginal tissue and into the systemic circulation in a dose-proportional manner, and there was little systemic accumulation...
January 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27278712/pharmacokinetic-and-pharmacodynamic-evaluation-of-the-drug-drug-interaction-between-isavuconazole-and-warfarin-in-healthy-subjects
#16
Amit Desai, Takao Yamazaki, Albert J Dietz, Donna Kowalski, Christopher Lademacher, Helene Pearlman, Shahzad Akhtar, Robert Townsend
This phase 1 trial evaluated pharmacokinetic and pharmacodynamic interactions between the novel triazole antifungal agent isavuconazole and warfarin in healthy adults. Multiple doses of isavuconazole were administered as the oral prodrug, isavuconazonium sulfate (372 mg 3 times a day for 2 days loading dose, then 372 mg once daily thereafter; equivalent to isavuconazole 200 mg), in the presence and absence of single doses of oral warfarin sodium 20 mg. Coadministration with isavuconazole increased the mean area under the plasma concentration-time curves from time 0 to infinity of S- and R-warfarin by 11% and 20%, respectively, but decreased the mean maximum plasma concentrations of S- and R-warfarin by 12% and 7%, respectively, relative to warfarin alone...
January 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27273461/pharmacokinetic-evaluation-of-cyp3a4-mediated-drug-drug-interactions-of-isavuconazole-with-rifampin-ketoconazole-midazolam-and-ethinyl-estradiol-norethindrone-in-healthy-adults
#17
Robert Townsend, Albert Dietz, Christine Hale, Shahzad Akhtar, Donna Kowalski, Christopher Lademacher, Kenneth Lasseter, Helene Pearlman, Diane Rammelsberg, Anne Schmitt-Hoffmann, Takao Yamazaki, Amit Desai
This report describes the phase 1 trials that evaluated the metabolism of the novel triazole antifungal isavuconazole by cytochrome P450 3A4 (CYP3A4) and isavuconazole's effects on CYP3A4-mediated metabolism in healthy adults. Coadministration of oral isavuconazole (100 mg once daily) with oral rifampin (600 mg once daily; CYP3A4 inducer) decreased isavuconazole area under the concentration-time curve (AUCτ ) during a dosing interval by 90% and maximum concentration (Cmax ) by 75%. Conversely, coadministration of isavuconazole (200 mg single dose) with oral ketoconazole (200 mg twice daily; CYP3A4 inhibitor) increased isavuconazole AUC from time 0 to infinity (AUC0-∞ ) and Cmax by 422% and 9%, respectively...
January 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27273343/pharmacokinetic-assessment-of-drug-drug-interactions-of-isavuconazole-with-the-immunosuppressants-cyclosporine-mycophenolic-acid-prednisolone-sirolimus-and-tacrolimus-in-healthy-adults
#18
Andreas H Groll, Amit Desai, David Han, Corrie Howieson, Kota Kato, Shahzad Akhtar, Donna Kowalski, Christopher Lademacher, William Lewis, Helene Pearlman, Debra Mandarino, Takao Yamazaki, Robert Townsend
This report summarizes phase 1 studies that evaluated pharmacokinetic interactions between the novel triazole antifungal agent isavuconazole and the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults. Healthy subjects received single oral doses of cyclosporine (300 mg; n = 24), mycophenolate mofetil (1000 mg; n = 24), prednisone (20 mg; n = 21), sirolimus (2 mg; n = 22), and tacrolimus (5 mg; n = 24) in the presence and absence of clinical doses of oral isavuconazole (200 mg 3 times daily for 2 days; 200 mg once daily thereafter)...
January 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27273248/pharmacokinetic-interaction-between-isavuconazole-and-a-fixed-dose-combination-of-lopinavir-400-mg-ritonavir-100-mg-in-healthy-subjects
#19
Takao Yamazaki, Amit Desai, David Han, Kota Kato, Donna Kowalski, Shahzad Akhtar, Christopher Lademacher, Laura Kovanda, Robert Townsend
This phase 1, open-label study evaluated the pharmacokinetic effects of coadministration of the antifungal agent, isavuconazole (administered as its water-soluble prodrug isavuconazonium sulfate), with the antiretroviral agent lopinavir/ritonavir in healthy adults. In part 1, 13 subjects were randomized to 2 arms to receive multiple doses of oral isavuconazole 100 mg either alone or with lopinavir/ritonavir 400/100 mg. In part 2, a different group of 55 subjects were randomized to 3 arms to receive multiple doses of oral isavuconazole 200 mg, either alone or with lopinavir/ritonavir 400/100 mg, or to receive oral lopinavir/ritonavir 400/100 mg alone...
January 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/27273149/pharmacokinetic-effects-of-isavuconazole-coadministration-with-the-cytochrome-p450-enzyme-substrates-bupropion-repaglinide-caffeine-dextromethorphan-and-methadone-in-healthy-subjects
#20
Takao Yamazaki, Amit Desai, Ronald Goldwater, David Han, Corrie Howieson, Shahzad Akhtar, Donna Kowalski, Christopher Lademacher, Helene Pearlman, Diane Rammelsberg, Robert Townsend
This report describes phase 1 clinical trials performed to assess interactions of oral isavuconazole at the clinically targeted dose (200 mg, administered as isavuconazonium sulfate 372 mg, 3 times a day for 2 days; 200 mg once daily [QD] thereafter) with single oral doses of the cytochrome P450 (CYP) substrates: bupropion hydrochloride (CYP2B6; 100 mg; n = 24), repaglinide (CYP2C8/CYP3A4; 0.5 mg; n = 24), caffeine (CYP1A2; 200 mg; n = 24), dextromethorphan hydrobromide (CYP2D6/CYP3A4; 30 mg; n = 24), and methadone (CYP2B6/CYP2C19/CYP3A4; 10 mg; n = 23)...
January 2017: Clinical Pharmacology in Drug Development
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