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Teng S.,PRACS Institute | Potvin D.,Theratechnologies | Mamputu J.-C.,Theratechnologies | Vincent G.,Theratechnologies | And 6 more authors.
Clinical Pharmacology in Drug Development | Year: 2013

The potential impact of tesamorelin on CYP3A activity was investigated by examining its effect on the pharmacokinetics of simvastatin and ritonavir. In two randomized, two-way crossover studies, subjects were administered 2mg tesamorelin on Days 1-7 with 80mg simvastatin or 100mg ritonavir co-administered on Day 6 (Treatment A), and a single dose of simvastatin or ritonavir alone on Day 6 (Treatment B). Pharmacokinetic samples were collected on Day 6 to measure simvastatin, ritonavir and tesamorelin plasma concentrations. For simvastatin, A/B ratios of least squares geometric means and corresponding 90% confidence intervals (CIs) for AUC0-t, AUC0-inf and Cmax were contained within the usual no effect range of 80-125%. For ritonavir, ratios and 90% CIs for AUCs were within this acceptance range, but the lower CI for Cmax was 74.8%, suggesting a decreased rate of exposure. However, since the A/B ratios for AUCs and Cmax parameters were approximately 90%, these were minor decreases and no dose adjustment of ritonavir is required in the presence of tesamorelin. These studies showed that the impact of tesamorelin on CYP3A activity appears to be minimal, if any. Either medication may be co-administered with tesamorelin in patients without changing their original dosing regimen. © The Author(s) 2013. Source

Demuth J.E.,University of Wisconsin - Madison | Ji Q.C.,Bristol Myers Squibb | Booth B.P.,Center for Drug Research and Evaluation | Fluhler E.N.,Pfizer | And 4 more authors.
Bioanalysis | Year: 2012

This University of Wisconsin School of Pharmacy bioanalytical conference is presented each year by the Extension Services in Pharmacy, the professional development department within the School. The purpose of this 4-day conference is to provide an educational forum to discuss issues and applications associated with the analysis of xenobiotics, metabolites, biologics and biomarkers in biological matrices. The conference is designed to include and encourage an open exchange of scientific and methodological applications for bioanalysis. To increase the interactive nature of the conference, the program was a mixture of lectures, poster sessions, round table discussions and workshops. This article summarizes the presentations at the 13th Annual Conference. © 2012 Future Science Ltd. Source

Clarke B.L.,Mayo Medical School | Kay Berg J.,PRACS Institute | Fox J.,NPS Inc | Cyran J.A.,NPS Inc | Lagast H.,NPS Inc
Clinical Therapeutics | Year: 2014

Background Impaired mineral homeostasis affecting calcium, phosphate, and magnesium is a result of parathyroid hormone (PTH) deficiency in hypoparathyroidism. The current standard of treatment with active vitamin D and oral calcium does not control levels of these major minerals. Recombinant full-length human PTH 1-84 (rhPTH[1-84]) is being developed for the treatment of hypoparathyroidism. Objective The goal of this study was to investigate the pharmacokinetics and pharmacodynamics of a single subcutaneous injection of rhPTH(1-84) in patients with hypoparathyroidism. Methods This was an open-label, dose-escalating study of single subcutaneous administration of 50 μg and then 100 μg of rhPTH(1-84). Enrolled patients (age range, 25-85 years) had ≥12 months of diagnosed hypoparathyroidism defined according to biochemical evidence of hypocalcemia with concomitant low-serum intact PTH and were taking doses ≥1000 mg/d of oral calcium and ≥0.25 μg/d of active vitamin D (oral calcitriol). The patient's prescribed dose of calcitriol was taken the day preceding but not on the day of or during the 24 hours after rhPTH(1-84) administration. Each patient received a single 50-μg rhPTH(1-84) dose, had at least a 7-day washout interval, and then received a single 100-μg rhPTH(1-84) dose. The following parameters were assessed: plasma PTH; serum and urine total calcium, magnesium, phosphate, and creatinine; and urine cyclic adenosine monophosphate. Results After administration of rhPTH(1-84) 50 μg (n = 6) and 100 μg (n = 7), the approximate t was 2.5 to 3 hours. Plasma PTH levels increased rapidly, then declined gradually back to predose levels at ~12 hours. The median AUC was similar with calcitriol and rhPTH(1-84) for serum 1,25-dihydroxyvitamin D (calcitriol, 123-227 pg·h/mL; rhPTH[1-84], 101-276 pg·h/mL), calcium (calcitriol, 3.3-3.7 mg·h/dL; rhPTH[1-84], 3.3-7.6 mg·h/dL), and magnesium (calcitriol, 0.7-0.9 mg·h/dL; rhPTH[1-84], 1.3-2.8 mg·h/dL). In contrast, the median AUC for phosphate was strongly negative with rhPTH(1-84) (calcitriol, -1.0 to 0.8 mg·h/dL; rhPTH[1-84], -21.3 to -26.5 mg·h/dL). Compared with calcitriol, rhPTH(1-84) 50 μg reduced 24-hour calcium excretion and calcium-to-creatinine ratios by 12% and 23%, respectively, and rhPTH(1-84) 100 μg reduced them by 26% and 27%. There was little overall impact on urine magnesium levels. Compared with calcitriol, rhPTH(1-84) 50 μg increased urinary phosphate excretion and phosphate-to-creatinine ratios by 53% and 54%, respectively, and rhPTH(1-84) 100 μg increased them by 45% and 42%. Urine cyclic adenosine monophosphate-to-creatinine ratio increased with rhPTH(1-84) by 2.3-fold (50 μg) and 4.4-fold (100 μg) compared with calcitriol. Conclusions PTH replacement therapy with rhPTH(1-84) regulated mineral homeostasis of calcium, magnesium, phosphate, and vitamin D metabolism toward normal in these study patients with hypoparathyroidism. © 2014 The Authors. Source

Gosai P.,PRACS Institute | Ducharme M.P.,Learn and Confirm Inc. | Ducharme M.P.,University of Montreal | Godfrey A.R.,PRACS Institute | And 6 more authors.
International Journal of Clinical Pharmacology and Therapeutics | Year: 2013

Introduction: Oxycodone is a semisynthetic opioid agonist used for the relief of moderate to severe pain. A new generic oxycodone hydrochloride (HCl) extended release (ER) tablet is currently being developed by Ranbaxy Pharmaceutical Inc., New Brunswick, NJ, USA. Objective: To assess relative bioavailability of a new generic (test) formulation of oxycodone hydrochloride (HCl) extended release (ER) tablets with that of marketed reference products, OxyContin® , in Canada and USA, in healthy adult subjects under fasting and fed conditions. Methods: Five studies were conducted in all, three of which were designed to comply with the regulatory criteria for marketing a new generic formulation of OxyContin® in Canada and the remaining two to comply with regulatory criteria for marketing a new generic formulation of OxyContin® in the USA. Each study was a balanced, randomized two-period, two-treatment, two-sequence, crossover design. A single oral dose of test or reference product was given in Period 1, followed by a 7-day washout period, after which subjects received the alternative product in Period 2. In order to block the pharmacological effects of oxycodone, subjects were administered naltrexone HCl (1 x 50 mg tablet) 12 hours prior to oxycodone HCl administration, concurrent with oxycodone HCl administration, and 12 hours after oxycodone HCl administration. Throughout the confinement portion of the study, adverse events were closely monitored. Serial blood samples were collected, following which oxycodone in plasma was estimated using a validated analytical procedure. Results: Oxycodone was well tolerated by subjects in both periods of each study under both fed and fasted conditions. No serious adverse events were observed. The ratios of geometric means for AUC0-t and Cmax and the affiliated 90% confidence intervals for AUC were within acceptance range recommended by Health Canada. These criteria were met for both the raw data as well as data corrected for measured drug content (potency). The ratios of geometric means and the 90% confidence intervals for AUC0-t, AUC 0-∞ and Cmax were within acceptance range recommended by United States Food and Drug Administration (FDA). Conclusions: Results demonstrate that the test formulation of oxycodone HCl ER tablets is bioequivalent to marketed OxyContin ® reference formulations in Canada and USA, when administered both under fasted and fed conditions. Additionally, oxycodone HCl ER tablets were well tolerated as a single oral dose when administered to healthy adult subjects under fasted and fed conditions. ©2013 Dustri-Verlag Dr. K. Feistle. Source

Nicholson R.,PPD Inc | Lowes S.,Quintiles | Caturla M.C.,Anapharm Europe | Safavi A.,BioAgilytix Labs | And 42 more authors.
Bioanalysis | Year: 2012

The 6th Global CRO Council for Bioanalysis (GCC) Closed Forum was held on 27 March 2012 in San Antonio, TX, USA, the day before the start of the 6th Workshop on Recent Issues in Bioanalysis. The attendance consisted of 45 bioanalytical CRO senior-level representatives on behalf of 37 CRO companies/sites from six countries. In addition to following up on the issue of co-administered drugs stability and on recommendations regarding the European Medicines Agency guideline, this GCC Closed Forum discussed topics of current interest in the bioanalytical field with focus on ligand-binding assays, such as lot changes for critical reagents, positive controls and reference standards, specificity for endogenous compounds, qualification and validation of biomarker assays, approach for biosimilars and criteria for LC-MS assays of small versus large molecules. © 2012 Future Science Ltd. Source

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