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Wilson C.G.,University of Strathclyde | Clarke C.P.,Icon Development Solutions Ltd. | Starkey Y.Y.L.,Glaxosmithkline | Clarke G.D.,Glaxosmithkline
Drug Development and Industrial Pharmacy | Year: 2011

Context: Acetaminophen (paracetamol, APAP) is widely used to relieve mild-to-moderate pain and reduce fever. Absorption of the drug can be impacted by dosage form; this may have implications for pain relief in some individuals, potentially accounting for suboptimal efficacy in analgesia. Objective: To assess the disintegration and dissolution of a new fast-dissolving acetaminophen tablet formulation (FD-APAP) and the impact on pharmacokinetic and pharmacodynamic parameters. Materials and methods: Two randomized, single-center, open-label, single-dose, two-way crossover studies in healthy subjects to compare FD-APAP (2× - 500mg tablets) with standard acetaminophen (2× - 500mg tablets). Gamma scintigraphy was used to assess tablet disintegration (Study 1, N=24), and plasma profiles were evaluated in the fasted state (Study 2, N=40). Results: In Study 1, the mean time to complete disintegration (12.9 vs. 69.6min, P<0.0001) and onset of disintegration were both significantly faster with FD-APAP than with standard acetaminophen (P<0.0001). For Study 2, median Tmax was significantly faster for FD-APAP (0.50 vs. 0.67h, P<0.01) and AUC0-30 min was significantly greater (4.51 vs. 2.74, P<0.05). AUC0-t and AUC0-inf were comparable between the two study treatments. Discussion: Despite the absence of comparative clinical data, the FD-APAP formulation may be expected to overcome some of the issues associated with the slow and variable absorption of standard acetaminophen tablet formulations, improving therapeutic outcome and avoiding the need to switch to alternative therapeutic options. Conclusion: Compared with standard acetaminophen, the FD-APAP formulation results in significantly faster onset of disintegration and more rapid absorption. © 2011 Informa Healthcare USA, Inc.


Vakkalagadda B.,Bristol Myers Squibb | Lubin S.,Bristol Myers Squibb | Reynolds L.,ICON Development Solutions LLC | Liang D.,ICON Development Solutions LLC | And 3 more authors.
Clinical Therapeutics | Year: 2016

Purpose This single-dose, open-label, randomized, 3-period, 3-treatment crossover drug–drug interaction study was conducted to evaluate differences in the pharmacokinetic properties of saxagliptin and dapagliflozin when coadministered. Methods Healthy subjects (N = 42) were randomized to receive saxagliptin 5 mg alone, dapagliflozin 10 mg alone, or saxagliptin 5 mg plus dapagliflozin 10 mg coadministered; there was a washout period of ≥6 days between treatments. Serial blood samples for determining saxagliptin, 5-hydroxy saxagliptin (5-OH saxagliptin; major active metabolite) and dapagliflozin plasma concentrations and pharmacokinetic parameters were collected before and up to 60 hours after the dose. No interaction was to be concluded if the 90% CIs for the geometric mean ratios of the combination compared with each drug given alone for Cmax and AUCinf were within 0.80 to 1.25. Findings The results indicated that dapagliflozin had no effect on the pharmacokinetic properties of saxagliptin, 5-OH saxagliptin, or saxagliptin total active moiety and vice versa. The 90% CIs for Cmax and AUCinf for all comparisons were contained entirely within the 0.80 to 1.25 equivalence intervals. Other pharmacokinetic parameters (apparent oral clearance or half-life) of saxagliptin or dapagliflozin were similar when each medicine was administered alone or when coadministered. No safety profile or tolerability findings of concern were observed during the study. All adverse events were mild, and no serious adverse events were reported. Implications These data indicate that coadministration of saxagliptin and dapagliflozin exhibits no pharmacokinetic interaction and is well tolerated. ClinicalTrials.gov identifier: NCT01662999. © 2016 Elsevier HS Journals, Inc.


PubMed | ICON Development Solutions LLC, Bristol Myers Squibb and Astrazeneca
Type: Journal Article | Journal: Clinical therapeutics | Year: 2016

This single-dose, open-label, randomized, 3-period, 3-treatment crossover drug-drug interaction study was conducted to evaluate differences in the pharmacokinetic properties of saxagliptin and dapagliflozin when coadministered.Healthy subjects (N = 42) were randomized to receive saxagliptin 5 mg alone, dapagliflozin 10 mg alone, or saxagliptin 5 mg plus dapagliflozin 10 mg coadministered; there was a washout period of 6 days between treatments. Serial blood samples for determining saxagliptin, 5-hydroxy saxagliptin (5-OH saxagliptin; major active metabolite) and dapagliflozin plasma concentrations and pharmacokinetic parameters were collected before and up to 60 hours after the dose. No interaction was to be concluded if the 90% CIs for the geometric mean ratios of the combination compared with each drug given alone for Cmax and AUCinf were within 0.80 to 1.25.The results indicated that dapagliflozin had no effect on the pharmacokinetic properties of saxagliptin, 5-OH saxagliptin, or saxagliptin total active moiety and vice versa. The 90% CIs for Cmax and AUCinf for all comparisons were contained entirely within the 0.80 to 1.25 equivalence intervals. Other pharmacokinetic parameters (apparent oral clearance or half-life) of saxagliptin or dapagliflozin were similar when each medicine was administered alone or when coadministered. No safety profile or tolerability findings of concern were observed during the study. All adverse events were mild, and no serious adverse events were reported.These data indicate that coadministration of saxagliptin and dapagliflozin exhibits no pharmacokinetic interaction and is well tolerated. ClinicalTrials.gov identifier: NCT01662999.

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