المؤلفون: Lubowski, T.J., Nightingale, C.H., Sweeney, K., Quintiliani, R.

المصدر: Clinical Pharmacokinetics ; volume 22, issue Supplement 1, page 43-47 ; ISSN 0312-5963

مصطلحات موضوعية: Pharmacology (medical), Pharmacology

الإتاحة: https://doi.org/10.2165/00003088-199200221-00008Test

المؤلفون: Mould, D. R., Sweeney, K., Duffull, S. B., Neylon, E., Hamlin, P., Horwitz, S., Sirotnak, F., Fleisher, M., Saunders, M. E., O'Connor, O. A.

المصدر: Clinical Pharmacology & Therapeutics; Aug2009, Vol. 86 Issue 2, p190-196, 7p, 3 Charts, 3 Graphs

مصطلحات موضوعية: HODGKIN'S disease, LYMPHOMAS, PHARMACOKINETICS, PHARMACOLOGY, FOLIC acid, PATIENTS

مستخلص: In a pralatrexate phase I study, patients displayed a high incidence of mucositis of grades 3 and 4. Preliminary evaluations of the pharmacokinetics of the drug and its association with mucositis suggested that pralatrexate exposure (area under the concentration–time curve (AUC)) could be controlled with body size (e.g., weight or body surface area)–based dosing and that pretreatment with folic acid and vitamin B12 might diminish the incidence and severity of mucositis. The study was amended, with revised dosing and vitamin B12 administration. Data from 47 patients were evaluated using NONMEM. Weight and methylmalonic acid (MMA) level were predictive of pharmacokinetic (PK) variability. AUC and MMA level were positively correlated with the risk of developing mucositis. A lower AUC schedule with vitamin B12 pretreatment may control mucositis without compromising efficacy. The covariates identified in this study are comparable with other antifolate analogs. The application of modeling was a critical step in the development of pralatrexate, yielding important suggestions for dose, scheduling, and pretreatment modifications.Clinical Pharmacology & Therapeutics (2009); 86, 2, 190–196 doi:10.1038/clpt.2009.80 [ABSTRACT FROM AUTHOR]

: Copyright of Clinical Pharmacology & Therapeutics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Malhotra, B. K., Glue, P., Sweeney, K., Anziano, R., Mancuso, J., Wicker, P.

المصدر: Clinical Pharmacology & Therapeutics; Mar2007, Vol. 81 Issue 3, p377-385, 9p

مصطلحات موضوعية: QUINOLONE antibacterial agents, PLACEBOS, ELECTROCARDIOGRAPHY, CLINICAL medicine, PHARMACOLOGY

مستخلص: The objective of our study was to determine the QTc effects of tolterodine. A crossover-design thorough QT study of recommended (2 mg twice daily) and supratherapeutic (4 mg twice daily) doses of tolterodine, moxifloxacin (400 mg once daily), and placebo was performed. Electrocardiograms (ECGs) and pharmacokinetic samples were obtained on days 1–4; time-matched baseline ECGs were taken on day 0. Mean placebo-subtracted change from baseline Fridericia-corrected QT (QTcF) during peak drug exposure on day 4 was the primary end point. Mean QTcF prolongation of moxifloxacin was 8.9 ms (machine-read) and 19.3 ms (manual-read). At recommended and supratherapeutic tolterodine doses, mean QTcF prolongation was 1.2 and 5.6 ms (machine-read), respectively, and 5.0 and 11.8 ms (manual-read), respectively. The QTc effect of tolterodine was lower than moxifloxacin. No subject receiving tolterodine exceeded the clinically relevant thresholds of 500 ms absolute QTc or 60 ms change from baseline. In conclusion, tolterodine does not have a clinically significant effect on QT interval.Clinical Pharmacology & Therapeutics (2007) 81, 377–385. doi:10.1038/sj.clpt.6100089 [ABSTRACT FROM AUTHOR]

: Copyright of Clinical Pharmacology & Therapeutics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Cooper, S. J., Sweeney, K. F., Toates, F. M.

المصدر: Psychopharmacology ; volume 63, issue 3, page 301-305 ; ISSN 0033-3158 1432-2072

مصطلحات موضوعية: Pharmacology

الإتاحة: https://doi.org/10.1007/bf00433567Test